Virology Test 2 Flashcards
What is the purpose of PCR?
Amplification of viral genome/DNA
What are the 3 steps of PCR?
Denaturation
Annealing
Extension/elongation
What are real-time PCR or quantitative PCR (qPCR)?
Advanced form of PCR which allows monitoring and quantification of increasing accumulation of PCR products/nucleic acid load as the reaction progresses.
Useful to study virus load in patients
What is DNA sequencing?
Process by which the sequence of bases in a DNA molecule is elucidated/can be obtained and read.
What are advantages to using Next generation sequencing?
Significantly cheaper Quicker Needs less DNA High throughput More accurate and reliable than Sanger sequencing
What is metagenomics?
The study of the collective set of microbial populations in a sample by analyzing the sample’s entire nucleotide sequence content, and is a powerful method for random detection of existing and new pathogens.
What is phylogenetic analysis?
The use of virus genome sequence data to study evolution of viruses and genetic relationships among viruses.
What is the advantage of microarrays in detection of pathogens in surveillance studies is?
Hundreds of pathogens can be screened for simultaneously using a single microarray chip.
What happens in a microarray?
Several thousand of known DNAs (probes), amplified by PCRs/RT-PCRs, are spotted onto a glass or a silicon chip.
The target/sample DNA are fluorescently labeled and then hybridized/added to the chip containing DNA probes.
Positive reactions between probe-DNA and sample DNA (hybridization) generate a fluorscent signal from the spot where probe DNA is spotted in the chip.
The study of virus evolution using genome sequence data is known as ______
Phylogenetics
Antiviral drugs
Class of medication used specifically for treating viral infections.
Interfere with the ability of a virus to infiltrate a target cell or target different stages of replication/synthesis of components required for replication of the virus
Immune system stimulation
Interferons, class of proteins that has antiviral effects and modulate functions of the immune system
What are the 3 ways/purposes of treating viral diseases?
Administer antiviral drugs.
Immune system stimulation.
Synthesize antibodies or administration of natural antiserum (antibodies).
Acyclovir antiviral activity is primarily restricted to________
Herpesviruses
What is Acyclovir as?
A prodrug, inactive form
What does acyclovir require in infected host cells to convert itself into active form and interfere with virus replication?
Virus enzymes
What is Acyclovir used to treat?
Herpesvirus infections in humans
Feline herpesvirus 1 induced corneal ulcers
Equine herpesvirus-1 induced encephalomyelitis
What is Acyclovir?
Synthetic nucleoside analog of deoxyguanosine.
Two main steps of mechanism of antiviral effect of acyclovir
Herpes simplex’s DNA polymerase enzyme incorporates the acyclovir monophosphate into the growing DNA strand as if it were 2-deoxyguanosine monophosphate (a “G” base). Further elongation of the chain in now impossible. Viral DNA chain synthesis stops.
Competitive inhibition of viral DNA polymerase, as acyclovir-triphosphate compete with dGTP for viral DNA polymerase.
Is acyclovir toxic to the uninfected host cell?
No
Why is acyclovir non-toxic to the uninfected host cell?
Since the enzymes herpesvirus thymidine kinase and herpes virus DNA polymerase are viral enzymes and not found in uninfected host cells, acyclovir cannot be phosphorylated and incorporated into the host DNA.
What does amantadine do?
Inhibits replication of most strains of influenza A viruses by blocking uncoating of the virus
What is the antiviral MOA of amantadine?
The M2 ion channel is the target of the antiviral amantadine.
These compounds clog the channel and prevent it from pumping protons into the virion.
In the presence of amantadine, viral RNAs remain bound to M1 and cannot enter the nucleus. Viral replication is inhibited.
Oseltamivir (Tamiflu) is what?
Inhibitor of neuraminidase (NA) enzyme synthesized by influenza A and B viruses.
Blocking the function of _________ with __ inhibitors is an effective way to treat influenza
Neuroaminidase; NA
Blocking the neuraminidase with NA inhibitors does what?
Prevents the release of virus and spread of infection, as the HA of virus is still bound/attached to the sialic acid containing receptors on the surface of already infected host cell.
Inhibition of neuraminidase slows _____ ____, giving the immune system the opportunity to “catch up” and mediate virus clearance.
Virus spread
What are two nucleoside analog reverse transcriptase inhibitors (NRTIs)
Zidovudine (ZDV) or AZT (Azidothymidine)
ddI (Didanosine)
What are ZDV/AZT?
Nucleoside analog of thymine, i.e. Resembles the deoxyribonucleotide containing the base thymine
What is the MOA of ZDV/AZT?
Competitive inhibition of reverse transcriptase activity: AZT-triphosphate competes with the thymine deoxyribonucleotide triphosphate for the reverse transcriptase.
Insertion of AZT-monophosphate into cDNA blocks the growth of the cDNA being transcribed from the viral RNA by reverse transcriptase.
AZT has been shown to reduce clinical signs of what when administered at a dose of 10mg/kg BID SQ for a period of 3 weeks?
FIV-positive cats
True/False: Acyclovir is a pro-drug?
True
_____ are required to cleave the HIV polyproteins into functional proteins
Proteases
Easy question
What inhibits the proteases?
Protease inhibitors
With protease inhibitors, HIV polyproteins can/cannot be cleaved into functional proteins?
Cannot.
How do protease inhibitors work?
Bind to the active site of the HIV protease and prevent the enzyme from cleaving HIV polyproteins into functional proteins. As a result, HIV can not mature and noninfectious viruses are produced
How are live-attenuated virus vaccines created? (4 ways)
From naturally occurring attenuated viruses.
Attenuation of virus by serial passage in cultured cells.
Attenuation of viruses by serial passage in heterologous hosts.
Attenuation of viruses by selection of cold-adapted mutations and reassortants.
What are non-replicating viral vaccines made?
Inactive whole virions.
Purified native viral proteins.
What is one more way/type of virus vaccines are made?
Produced by recombinant DNA and related technologies
True/False: DIVA stands for Differentiating infected from vaccinated animals
True
MOA of DIVA
Subunit ‘marker vaccine’ DIVA vaccines have only a portion (subunit) of the pathogen in the vaccine i.e. Has less antigens than natural strains.
If antibodies to other parts/antigens of the pathogen no included in the vaccine are detected the animal has been infected with the pathogen.
If only antibodies to the vaccine subunit/antigens are detected, the animal has not been infected.
An accompanying diagnostic test allows us to actually make the differentiation.
Isolation
Applies to animals/persons who are known to be ill with a contagious disease. Separate animal if they show clinical signs and/or test positive by diagnostic test.
Quarantine
Applies to those who have been exposed to a contagious disease.
Separate animal if exposed to a contagious disease, even if it does not show clinical signs, and/or animal test negative by diagnostic test.
Quarantine and Culling
To separate and restrict the movement of animals.
Culling of animals.
Proper disposition of culled animals.
Decontamination
Term used to describe a process or treatment that renders a medical device, instrument, or environmental surface safe to handle.
Sterilization
A process that destroys or eliminates all forms of microbial life/pathogens, including highly resistant pathogens, such as bacteria with spores.
Disinfection
A process that eliminates many or all pathogenic microorganisms, except bacterial spores, on inanimate objects.
Less effective than sterilization, does not necessarily kill all microorganisms.
Antisepsis
Application of a liquid antimicrobial chemical to skin or living tissue to inhibit or destroy microorganisms.
What are the sterilization methods?
Moist heat: autoclave.
Dry heat: hot air oven
Chemical methods: gases like ethylene oxide, ozone
Radiation: non-ionizing - UV radiation; ionizing - gamma rays, x-rays
Sterile filtration: microfiltration using membrane filters
Vaccines produced by serial passage of viruses in heterologous hosts is a ______
Live-attenuated vaccine
True/False: Quarantine and isolation have the same meaning
False
Autoclave is a method of _________
Sterilization
What is the family of poxviruses?
Poxviridae
What is the subfamily of Poxviridae?
Chordopoxvirinae
How many genera are there for the pox virus?
8
What are the 6 genera important for our class on pox virus?
Orthopoxvirus Parapoxvirus Avipoxvirus Capripoxvirus Leporipoxvirus Suipoxvirus
Properties of Poxviruses
Large, sometimes enveloped, DNA viruses with complex structure.
Most are pleomorphic, typically brick-shaped. Possess an irregular surface of projecting tubular or globular structures.
Members of the genus Parapoxvirus are ovoid, covered with long thread-like surface tubules, which appear to be arranged in crisscross fashion, resembling a ball of yarn.
What are the two distinct infectious poxvirus particles that exist?
Intracellular mature virus (IMV)
Extracellular enveloped virus (EEV)
T/F: both IMV and EEV are infectious
True
EEV contains 2 membranes:
Envelope
Inner membrane
How do virions acquire the extra envelope?
Cells released by budding.
The envelope contains virus encoded-proteins from host cell membrane.
IMV have how many membranes?
1
Only inner membrane; come out by disruption of host cells.
T/F: Poxviruses conform to the icosahedral or helical symmetry.
False
Complex symmetry
The virion outer layer encloses a ________-shaped core and two lateral bodies
Dumbbell
What is contained in the core of a poxvirus?
Viral DNA with several proteins
May have more than 200 genes in their genome, and as many as 100 of these encode proteins that are contained in virions
The genome of poxviruses consists of
Single molecule of linear ds DNA
Many proteins encoded by the poxvirus are enzymes involved in ______ _____ synthesis and virion structural components
Nucleic acid
Also encode proteins that specifically counteract host adaptive and innate immune responses
Where does replication of the poxvirus occur?
Predominantly in the cytoplasm
How is it possible that the poxvirus replicates in the cytoplasm?
Have evolved to encode the enzymes required for transcription and replication of the viral genome.
How are poxviruses released after replication?
Budding
Exocytosis
Cell lysis
Most virions are not enveloped and are released by ____ _______
Cell lysis
T/F: Enveloped virions are taken up by cells more readily and appear to be more important in the spread of virions through the body of the animal
True
Stability of poxviruses
Virion is enveloped particle.
High environmental stability, remain infectious over a period of several months in ambient environment.
Low lipid content - less sensitive to organic solvents/disinfectants.
High resistance to drying
Can survive many years in dried scabs or other virus-laden material.
Poxvirus transmission
Skin: cannot infect intact skin. Contact of infectious material with broken or lacerated skin is a common route of poxvirus transmission.
Respiratory route: some by aerosol route (sheeppox)
Mechanically: arthropods (Myxoma virus and avipoxviruses
Pathogenesis and Immunity to poxvirus
Epitheliotropic causing cutaneous lesions
Sometimes cause systemic diseases in birds and wild animals
Many are host specific
Orthopoxviruses infect a wide range of species
Spread of poxvirus
Following introduction into the body, poxvirus usually gains access to the systemic circulation via the lymphatic system.
A secondary viremia disseminates the virus back to the skin and to other target organs.
What is the pathway of skin lesions in poxvirus infection?
Macule-> papule -> vesicle -> pustule -> scab -> scar
What is a macule
Flat and red. Local inflammation immune response infiltrating leukocytes
What is a papule?
Raised and red. More marked inflammation (invasion of neighboring tissue)
What is a vesicle?
Small blister: microbe invades epithelium
T/F: Ulceration will never develop with poxvirus lesions
False
They are possible
Rupture of the ______ from poxvirus can predispose to secondary bacterial infections
Pustules
Distribution of cowpox
Endemic only in Europe and Asia
Hosts of cowpox
Cattle
Wild and domestic cats
Humans
Zoo animals
Reservoir host of cowpox
Rodents
Transmission of cowpox in cattle
Infected milker’s hands or teat cups
Infected farm cats
Rodents
Economic importance of cowpox in cattle
Losses to farmers due to inconvenience in milking b/c of soreness of teats and mastitis resulting from secondary bacterial infections
Clinical findings with cowpox in cattle
Mildly febrile, papule appear on teats and udders
Sucking calves may develop lesions in mouth
Vesicles may not be evident or may rupture readily leaving ulcerated areas that form scabs
Transmission of cowpox in cats
Skin inoculation - bit or skin wound
Rodents
Oro-nasal route
Pneumonia in exotic felids
Primary lesions of cowpox in cats
Primary skin lesion - head, neck or forelimb
May form small, stabbed wound to large abscess
Secondary lesions of cowpox in cats
After primary, widespread secondary appears.
2-4 days - discrete, circular, ulcerated papules that are .5-1 cm in diameter.
Ulcers covered by scabs and healing is usually complete by 6 weeks.
Many cats show no signs other than skin lesions, ~20% develop mild coryza or conjunctivitis.
Complications fro secondary bacterial infection
Transmission of cowpox in humans
Cuddly cats
Rarely from rodents and zoo animals
Less likely from cattle
Clinical signs of cowpox in humans
Macropapular lesions on hands and face -> vesicular and ulcerative lesions. Enlarged painful local lymph nodes Fever Vomiting Sore throat
Monkeypox in humans
Viral zoonosis with symptoms in humans similar to those seen in the past in smallpox patients
Transmission of monkeypox in humans
Primary - direct contact with blood, bodily fluids, or rashes of infected animals. In Africa, human infections have been documented through the handling of infected monkeys, Gambian rats or squirrels.
Secondary- human to human. Close contact with infected respiratory tract excretions, with the skin lesions of an infected person or with recently contaminated objects
Pseudocowpox: que es?
Viral skin disease that causes mild sores on the teats and udders of cattle.
Can also infect humans and condition is commonly referred to as milker’s nodules.
Etiology of pseudocowpox
Member of the genus parapoxvirus
Epidemiology of pseudocowpox
Reported from most countries
Transmission of pseudocowpox
Infected cattle Contaminated milker's hands, teat cups Biting insects Calves get during suckling Semen of bulls
Pathogenesis of pseudocowpox
Hyperplasia of squamous epithelium
Clinical signs of pseudocowpox
General mild
Acute lesions of pseudocowpox
Erythema -> papules -> vesicle or pustule -> rupture -> thick scab
Thick scab (.5 to 25 cm) becomes elevated due to accumulation of granulation tissue. 7-10, scab falls off leaving horseshoe-shaped ring of small scabs surrounding a small wart-like granuloma
Chronic lesions of pseudocowpox
Starts as erythema Yellow-gray, soft scurfy scabs which are rubbed off during milking Skin is corrugated No pain Lesions may persist for months
Diagnosis of pseudocowpox
Horseshoe-shaped ring like lesions are pathognomonic.
Isolation and detection of the virus by various diagnostic lab methods from vesicular fluid or from teat skin.
Differential diagnosis of pseudocowpox
Cowpox virus Bovine herpesvirus ulcerative mammalitis Vesicular stomatitis Udder impetigo (bacterial dermatitis characterized by the development of small pustules on the skin of the udder and teats) Teat chaps and frostbite Black spot (a form of hyperkeratosis)
Treatment of pseudocowpox
Removal of scabs
Burn the scabs to prevent environmental contamination
Application of emollient ointment before milking
Application of astringent preparation after milking
Prevention of pseudocowpox
Disinfection - use iodophor teat dip
Isolation and treatment of infected cows
Reduce teat trauma, as injuries to skin of teat predisposes to infection
Pseudocowpox in humans or Milker’s nodules
Causes a mild skin lesion known as Milker’s Nodules
Lesions on the hands of dairy farmers milking teats or vets treating infected cows
Lesions may vary from multiple vesicles to a single, indurated nodule
What is the etiology of Contagious ecthyma, ORF?
Orf virus, Genus Parapoxvirus
Who is the host of ORF?
Sheep and goat. Primarily in lambs and goat kids
What is the distribution of ORF?
Worldwide
Transmission of ORF?
Scabs that fall off from the healing lesions contain virus.
Virus are stable in the environment, i.e remains highly infectious for long periods under dry conditions.
Contaminated instruments, like docking instruments or ear-tagging plier can transmit virus.
Spread in flock in rapid.
Virus infects healthy animals primarily through damaged skin.
Oral lesions in lambs or kids result from nursing dams with teat lesions, and vice-versa.
Pathogenesis of contagious ecthyma (ORF)
Damage of skin is essential to establish infection.
The skin reaction to viral infection consists of a cellular response with necrosis and sloughing of the affected epidermis and underlying stratum papillary of the dermis.
The cutaneous response to infection includes a delayed-type hypersensitivity reaction and an influx of inflammatory cells.
The lesions evolve from macule -> papule -> vesicle -> pustule ->ulcers -> scab formation.
Clinical signs of orf
First lesions develop in the mucocutaneous junction and are accompanied by swelling of the lips.
From there, lesions spread to the muzzle and nostrils, surrounding hairy skin and the buccal mucosa.
Animals may find it difficult to take food because of oral lesions: anorexia and weight loss
Infected lambs or kids sucking ewes or goats may result in lesions on teats.
They may predispose to secondary bacterial infection = mastitis.
Severe cases show what clinical signs of ORF?
May show in genitals, coronets (feet), and ears.
Lesions in feet result in lameness.
Lesions in scrotum leads to infertility.
The scabs from orf drop off and the underlying tissues heal. But what can happen to the skin after?
Complications from secondary infection, or from invasion of lesions by fly larvae.
A malignant form of the disease has also been observed in sheep.
Vaccination of ORF
Prepared from suspension of scabs in glycerol saline and is painted onto a small area of scarified skin inside the thigh, where a localized lesion develops.
The vaccine should NEVER be used on farms that do not have a problem with orf.
Inspect the lamb 1 week after vaccination for local reactions, which indicates the viability of the vaccine.
Vax do not offer long-lasting immunity, ~1-2 years
T/F: in problem flocks/herds, the lambs/kids may need to be vaccinated
True
Pregnant ewes should be vaccinated before/after lambing
Before
ORF in humans
Macro-popular lesions and large nodular lesions in finger, hand, arm, face and even the penis.
Secondary bacterial infections of lesions may cause complications
Etiology and distribution of sheeppox and goatpox
E: members of the Genus Capripoxvirus
D: Endemic in Africa, Asia and parts of Europe
Sheep pox virus (SPV) and goat pox virus (GPV) were once believed to be strains of the same virus, but ____ ________ has now demonstrated them to be separate viruses
Genetic sequencing
T/f: most strains of sheep and goat pox are host specific and cause severe clinical disease in either sheep or goats, while some strains have equal virulence in both species
True
Can SPV and GPV be distinguished from each other with serological techniques, including viral neutralization
No sir they cannot
SPV and GPV are closely related to what viral disease of cattle? Is there evidence of this virus infecting sheep and goats?
Lumpy skin disease virus (LSDV)
No
Transmission of sheeppox and goatpox
Highly contagious
Enters by respiratory tract - aerosol route***
Through mucous membrane or abraded skin, especially by direct contact with contaminated iatrogenic materials
Virus is present in nasal and oral secretions for several weeks after infection
Can survive in dry scabs for months
Evidence of mechanical transmission by biting arthropods
Pathogenesis of sheeppox
Systemic disease**
Incubation period is followed by a leukocyte-associated viremia.
Localizes in skin and other internal organs
Deposition of the immune-complexes (of sheeppox) results in what and where does it develop?
Severe necrotizing vasculitis develops in arterioles and postcapillary venules of skin.
Results in ischemic necrosis of dermis and overlying epidermis
What are the two forms of sheeppox
Malignant
Benign
Malignant form from sheeppox
In lambs and susceptible nonnative breeds.
Pox lesions develop on skin and buccal, respiratory, digestive and urinary tract mucosa.
Cutaneous nodules are distributed widely over body- occasionally become vesicular, pustular and finally scabs.
Lesions heal leaving star-shaped scar free of hair or wool
The lesions from malignant sheeppox can spread from primary regions to?
Pharynx Larynx Lungs Vagina Abomasum Spleen
Secondary pneumonia common
Abortion rare
The mortality and case fatality rate of malignant sheeppox is high/low.
High
Benign form of sheeppox
More common in adults and resistant breeds
Only skin lesions occur
None to mild systemic reactions
Prevention and control of sheeppox
Notifiable disease in most countries of the world
Are vaccines available for sheeppox?
Yes, a large variety of commercial vaccines are available including subunit vaccines.
Killed vaccines elicit temporary protection at best.
Live attenuated vaccines offer excellent protection >1 year
Where is Goatpox found?
Africa
Asia
parts of Europe
Is goatpox reportable?
Yes
Goatpox disease is clinically similar to?
Sheeppox
Age group affected by goatpox systemic disease
Young kids
Age group affected by mild forms of goatpox
Adults
Etiology of lumpy skin disease
Members of genus Capripoxvirus
Distribution of lumpy skin disease
Enzootic in sub-Saharan Africa and Middle East with recent incursion in Iraq
Transmission of lumpy skin disease
Arthropod vector
Direct contact
Host of lumpy skin disease
Cattle
All ages and types susceptible
Clinical findings of lumpy skin disease
Fever
Multiple nodular lesions on skin and mucus membranes
Lymphadenopathy
Etiology of swinepox
Members of genus Suipoxvirus
Distribution of swinepox
Worldwide
Widespread, sporadic disease
Hosts of swinepox
Cattle
JK, making sure you’re paying attention.
Pigs
Benign with low mortality and morbidity in older.
High case fatality in congenitally infected and very young sucking piglets
Transmission of swinepox
Direct contact associated with skin injury, can live in scab for years.
Mechanical transmission - pig louse or Haematopinus suis. Lice can carry virus for weeks-months. Also flies and insects.
For swinepox, there is evidence of ________ infection in neonatal pigs
Transplacental
What are the typical pox lesions of swinepox?
Skin lesions occur anywhere, most obvious on abdomen and inner thighs. Exudative epidermitis (greasy pig disease) and secondary bacterial dermatitis occasionally follow swine pox. Severe infections, especially in congenitally-acquired pox infections can have lesions occur in upper respiratory and digestive tracts
Control of swinepox
Eradication of lice from piggery
No commercially available vaccine
Etiology of fowlpox
Genus Avipoxvirus
*first virus grown in embryonated eggs
Hosts of fowlpox
Poultry and turkeys
Are turkeys not poultry?
Distribution of fowlpox
Worldwide
Transmission of fowlpox
Extremely resistant to desiccation
Can survive in exfoliated scabs for long time.
Transmitted within flocks through minor wounds and abrasions of mouth, comb, wattles, or skin from fighting or pecking each other.
Mechanically by mosquitoes, lice and ticks.
Possibly aerosol
What are the 3 forms of fowlpox disease
Cutaneous (dry)
Diphtheritic (wet)
Ocular
The cutaneous or dry form of fowlpox
Most common
Low mortality
Results from biting arthropods or mechanical transmission to injured or lacerated skin
Small papules on comb, wattles and around beak
Occasionally lesions on legs, feet and cloaca
Nodules become yellowish and thick scab
Sharp fall in egg production
T/F: in uncomplicated cases of cutaneous form of fowlpox, the affected birds recover
True
Diphtheritic (wet) form of fowlpox
Probably caused by droplet infection.
Involves infection of mucous membranes of mouth, pharynx, larynx, and sometimes trachea.
Coalescing lesions result in necrotic pseudomembrane -> death by asphyxiation.
Prognosis is poor.
Ocular form of fowlpox
Conjuntivitis
Cheesy exudate accumulates under eyelids
What are Bollinger bodies of avipoxvirus?
Eosinophilic granular intracytoplasmic inclusion bodies.
What are Borrel bodies of avipoxvirus?
Occur inside Bollinger bodies. Are minute spherical bodies obtained by tryptic digestion of Bollinger bodies.
Vaccination for fowlpox control
Modified live fowlpox or pigeon pox virus vaccines of chicken embryo or avian cell culture origin are available commercially.
Recombinant fowlpox vectored vaccines have been developed.
Other than vaccines, what’s another method of fowlpox control?
Control mosquito population and other biting insects
Transmission of ulcerative dermatosis of sheep (unclassified poxvirus)
Infection through damaged skin or by coitus
Clinical forms of ulcerative dermatosis of sheep
Usually ulcers with raw crater that bleeds easily
Ulcerative dermatosis of sheep manifests in what two clinical forms?
Lip and les ulceration
Venereal form: ulceration of the prepuce and penis or vulva. Ram becomes unfit for natural breeding.
How do we diagnose poxviruses?
Clinical signs
Sample material: scrapings from skin lesions, vesicular fluid, crusts, scabs
Electron microscopy: characteristic morphology and size of poxviruses. Orthopoxviruses are brick shaped. Parapoxviruses are ovoid.
Serological assays (ELISA) Detection of poxvirus nucleic acid by PCR
How do we use histopathology to diagnose poxvirus?
To see presence of characteristic intracytoplasmic inclusion bodies.
Type-A
Type-B
Bollinger and Borrel bodies
What are Type-B (Guanrnierei) inclusion bodies?
Induced by most poxviruses.
Slightly basophilic
Composed of viral particles and protein aggregates.
What are Type-A (ATI) inclusion bodies
Induced by some poxviruses - cowpox and ectromelia virus.
Strongly eosinophilic
Can we inoculate embryonated eggs to diagnose poxviruses?
Yes
Chorioallantoic membrane -> pock lesions.
*Parapoxviruses do NOT multiply in chicken embryo
What two viruses are we talking about under the family Circoviridae, genus Circovirus?
Porcine circovirus type-1 (non-pathogenic)
Porcine circovirus type-2 (post-weaning multisystemic wasting syndrome [PMWS])
What virus is under the family Circoviridae, genus Gyrovirus?
Chicken infectious anemia virus
What are the viruses with circular single-stranded DNA genomes? What are the differences?
Circovirus: ambisense DNA
Gyrovirus: negative sense DNA
What virus has 12 trumpet-like structures that are less obvious in the other circoviruses?
Chicken infectious anemia virus
Virus replication occurs in what type of cells for Circoviridae?
Actively dividing cells
Where does DNA replication occur?
Nucleus
T/F: Circoviridae virions are not very stable
False
Etiology of post-weaning multisystemic wasting syndrome (PMWS)
Porcine circovirus 2 (PCV2)
Hosts of PMWS
Pigs
Most common 4-6 weeks or 2-3 weeks post-weaning
Transmission of PMWS
Wide-spread
Fecal-oral: most common method
Vertical transmission (transplacental infection)
Pathogenesis of PMWS
Individual coalescing foci of granulomatous inflammation in lymphoid tissue, lungs, liver, kidney, heart and intestines; sometimes with prominent “botryoid” (grape-like) intra-cytoplasmic inclusion bodies in virus infected macrophages
What is lymphoid depletion?
Loss of B-cells and T-cells
Transplacental infection of PMWS
Infection during the first and second trimesters results in fetal death and resorption or aborted fetuses with severe cardiac congestion. Infection during last trimester has minimal effect of fetuses
Clinical signs of PMWS
Subclinical infection most common. Lethargy Progressive weight loss Cough Dyspnea Slow growth Lymphadenopathy Diarrhea Skin discoloration Congenital tremors Icterus (less common
PMWS commonly gets a co-infection with which viruses?
Porcine parvovirus (PPV)
Porcine reproductive and respiratory virus (PRRSV)
SIV
Mycoplasma hyopneumonea
Other opportunistic bacteria that may cause severe disease and more pronounced lesions
Diagnosis of PMWS
Serological assays: most pigs are seropositive so antigen detection is not of much value
Vaccines for PMWS
Chimeric vaccines: use non-pathogenic porcine circovirus 1 (PCV-1) as a genetic backbone for expression of the immunogenicity capsid protein of PCV-2.
Inactivated or baculovirus-expressed vaccines: virus-like particles include the capsid protein of PCV-2
Sow vaccination antepartum
Porcine dermatitis and nephropathy syndrome (PDNS)
Associated with PCV2
Sporadic
Reported in older piglets
Findings:
Necrotizing skin lesions
Necrotizing vasculitis
Necrotizing and fibrinous glomerulonephritis
What is Gyrovirus cause?
Chicken infectious anemia
Host of chicken infectious anemia
Highly contagious disease of young chickens (2-4 wo)
Older chickens more resistant
Transmission of chicken infectious anemia
Virus is shed in feces and feather dander
Horizontal transmission is through inhalation or oral exposure
Virus is also transmitted vertically through egg
Pathogenesis of chicken infectious anemia
Replication in hemocytoblasts in bone marrow, precursor T cells in the cortex of the thymus, and dividing CD4 and CD8 cells in spleen
Apoptin protein of CAV virus induce apoptosis
Immunosuppression and aplastic anemia
Vulnerable to secondary bacterial and fungal infections
Replication in oviduct regulated by estrogen allowing more efficient vertical transmission
Clinical signs and lesions of chicken infectious anemia
Anorectic Lethargic Depressed Reduced body weight gain Pale Thrombocytopenia: watery blood with slow clot PCV low SQ hemorrhages and skeletal hemorrhages Pale muscles
Differences in anatomy with chicken infectious anemia
CAV-induced thymic atrophy
Pale, aplastic bone marrow
Pale carcass
Atrophied bursa
Diagnosis of chicken infectious anemia
Examination of blood: low PCV
Examine blood for total erythrocytic count will reveal anemia
Thrombocytopenia
Blood watery with slow clot
Vaccination for chicken infectious anemia
Presence of antibodies in breeders greatly reduced vertical and horizontal transmission
Protect progeny from vaccinated breeders from early infections by means of maternally derived antibodies
Live vaccines available: antibody-negative breeder flocks before the start of egg production
T/F: Herpesviridae are enveloped, spherical to pleomorphic viruses
True
Do Herpesviridae have ss or ds DNA?
ds
Viral replication of Herpesviridae
DNA replication and encapsidation occur in nucleus
Viral envelope is acquired by budding through the inner layer of nuclear envelope
Mature virions accumulate within vacuoles in cytoplasm and are released by exocytosis or cytolysis
Do Herpesviruses survive well outside of the host cell?
Nope to the nope nope
Moist, cool environmental conditions promote extended survival of herpesviruses.
Latently infected animals serve as a reservoir for transmission
T/F: Persistent infection with periodic or continuous shedding occurs in only a few herpesvirus infections
False, all of them
T/F: herpesviruses are oncogenic
True
Reactivation of latent herpesvirus infection is usually associated with _____ caused by intercurrent infections, shipping, cold, crowding or by the administration of __________ drugs
Stress; glucocorticoid
What type of inclusion bodies belong to Herpesviruses?
Eosinophilic intranuclear
Known as type A Cowdry bodies
T/F: Herpesviruses can cause syncytium
True
What are the properties of Alphaherpesvirinae?
Generally highly cytopathic in cell culture
Relatively short replication cycle
T/F: some alphaherpesviruses, like pseudorabies virus) have a narrow host range, whereas most are highly restricted in their natural host range.
False, broad host range
Where do most localized lesions occur from alphaherpesviruses?
Skin
Mucosa of the respiratory and genital tracts
(Alphaherpesviruses) Generalized infections characterized by foci of necrosis in almost any organ or tissue are typical of infection of ______ or ______ animals.
Very young; immunocompromised
In pregnant animals, alphaherpesvirus cross the placenta, leading to ______, characteristically with multifocal areas of necrosis in several fetal organs.
Abortion
There are 3 subtypes of bovine herpesvirus 1 (BHV-1) but what are the 2 important ones for this class?
BHV-1.1 (respiratory subtype)
BHV-1.2 (genital subtype)
Transmission of BHV
Respiratory disease and conjunctivitis result from droplet transmission
Genital disease may result from coitus or AI with infective semen.
Pathogenesis of BHV
In both genital and respiratory forms of the disease, lesions are focal areas of epithelial cell necrosis in which there is ballooning of epithelial cells.
Typical herpesvirus inclusions may be present in the nuclei at the periphery of necrotic foci.
Intense inflammatory response within the necrotic mucosa, frequently with formation of an overlying accumulation of fibrin and cellular debris (pseudomembrane)
T/F: life-long latent infection with periodic virus shedding occurs after BHV-1 infection
True
T/F: All seropositive animals are considered as potential carriers.
True
T/F: BHV cannot be reactivated from latency by corticosteroids or stress
False, they can be
Where are the sites of latency for BHV?
Trigeminal nerve: respiratory disease with BHV-1.
Sciatic nerve: genital disease with BHV-1
Clinical signs of BHV
Respiratory form (red nose, necrotic rhinitis, dust pneumonia):
Rhinitis
Laryngitis
Tracheitis
Clinical signs for the respiratory BHV form
Inflamed nares gives the appearance of having a “red nose” due to hyperemia
Grayish necrotic foci on the mucous membrane
Nasal discharge becomes more profuse and mucopurulent
Uncomplicated cases recover in 10-14 days
Respiratory BHV may result from secondary bacterial infections such as? Death is usually a result of?
Mannheimia hemolytica and Pasteurella multocida (shipping fever)
Secondary bronchopneumonia
Ocular form of IBR
Conjunctivits is a common finding in typical “red nose”
Do not misdiagnose BHV as what?
Pink-eye or infectious bovine keratoconjunctivitis.
IBR lesions are confined to the conjunctiva and no lesions on cornea except diffuse edema.
Abortion caused by BHV-1
Occurs as a common sequel to natural infection
Result of some modified-live virus (MLV) vax being given to pregnant animals.
Animals in contact with IBR-susceptible pregnant animals.
Fetuses in second half of gestation have a higher incidence of abortion but early embryonic death is possible
Often preceded by pustular vulvovaginitis
BHV-1 causing systemic disease of newborn calves
Severe in calves less than 10 days of age
Often fatal
Infected in-utero or right after birth
Genital disease from BHV-1: IPV (infectious pustular vaginitis)
After coitus
Frequent urination
Tail is usually held in an elevated position and excessive tail switching is noted
Vagina mucosa red and swollen
Mild vaginal discharge
Vulva swollen, red spots and discrete pustules may be noted
BHV-1 genital disease: balanoposthitis
Inflammation and pustules in the mucosa of the penis and prepuce
Control (vaccination) of BHV
Modified live vax, subunit and inactivated vax are available
Parenteral and intranasal vax available
Both stimulate the production of humoral antibodies
The parenteral vax may cause abortion in pregnant cows.
Intranasal vax is safe for use in pregnant cows
What two diseases are caused by BHV-2
Bovine ulcerative mammalitits
Pseudo-lumpy skin disease
Host of bovine ulcerative mammalitis
Cattle
Heifers
Usually within 2 weeks after calving (persistent disease)
Transmission of Bovine ulcerative mammilitis
Direct contact and fomite-mediated, through skin trauma
Mechanical transmission by stable flies and other arthropods
Clinical signs of bovine ulcerative mammilitis
Severe cases: teats swollen and painful Skin is bluish Exudes serum Formation of raw ulcers High incidence of mastitis
Pseudo-lumpy skin disease
Cattle are infected
Occurs most commonly in Southern Africa
Mechanical transmission of the virus occurs by arthropods
Clinical signs of pseudo-lumpy skin disease
Mild fever followed by sudden appearance of skin nodules: few or many, on face, neck, back, and perineum
What disease is caused by Porcine herpesvirus 1/Suid herpesvirus 1 (belong to subfamily Alphaherpesvirus)
Pseudorabies (Aujeszky disease, Mad itch)
Etiology of Pseudorabies
Porcine herpesvirus 1/Suid herpesvirus 1
Hosts of pseudorabies
Primarily swine
Secondary: Horse Cattle Sheep Goats Dogs Cats Many feral species
Humans are refractory to infection
Transmission of pseudorabies in primary hosts
Recovered pigs act as primary reservoirs, and are latent carriers for life.
Rodents can be reservoirs and transmit disease from farm to farm.
Routes:
She’d in saliva, nasal discharges and milk of infected pigs
Not shed in urine or feces
Licking, biting, aerosol, ingestion of contaminated carcass, water and feed.
Transmission of pseaudorabies in secondary hosts
Dogs and cats: ingestion of infected pig carcass/meat, or rodents
Cattle: direct contact with infected pigs, oral and nasal routes
Pathogenesis of pseudorabies
Primary site of viral replication is upper respiratory tract
Spread of pseudorabies
Virus replicates in tonsils and nasopharynx
Spreads via the lymphatics to regional lymph nodes, where replication continues
A brief viremia is associated with virulent strains, with localization of virus in different organs
Pseudorabies virus spread in CNS
Via axons of cranial nerves
Preference for neurons and the pons and medulla
CNS lesions due to pseudorabies
Ganglioneuritis
Nonsuppurative meningoencephalitis
Perivascular cuffing
Clinical signs of pseudorabies
Nonimmune piglets: 100% mortality rates
Nonimmune pregnant sows: ~50% abortion rate
Older piglets, growers, and adult pigs: mild disease, mortality <2%
Pruritus (itching), a dominant feature in secondary hosts, is rare in pigs
Piglets born to nonimmune sows with pseudorabies
Most susceptible
Signs of CNS disease (in coordination of hindlimbs, fitting, tremors, and paddling) are more commonly seen
Weaned pigs and growing pigs with pseudorabies
CNS signs may be reduced and an increase in respiratory signs
Nonimmune pregnant sows with pseudorabies
Infection before 30 days of gestation result in death and resorption of embryo.
Infection in late pregnancy may result in mummified, macerated, stillborn, weak or normal swine.
Up to 20% of sows aborting are infertile on next breeding, but eventually conceive
Necropsy findings of swine with pseudorabies
Gross lesions are often absent or minimal
Serous to fibrinous rhinitis is common and a necrotic tonsillitis
Clinical signs of pseudorabies in secondary hosts
(Ruminants, dogs, cats, horses)
Intense pruritus
Hyperacute
Rapid progress
High mortality
Cattle with pseudorabies
Aka Mad itch Intense pruritus Cattle may become frenzied Progressive involvement of CNS, stage of paralysis, ataxia Death from respiratory failure
Dogs and cats with pseudorabies
Dogs:
Frenzy associated with pruritus, self-mutilation
Paralysis of jaws and pharynx with drooling
Plaintive howling
Dogs do not tend to attack
Cats:
Progress is so rapid that pruritus may not be observed
Vaccination of pseudorabies
Vax of swine in enzootic areas reduce losses.
Vax do not prevent infection, or establishment of latent infection by wild-type virus, but can alleviate clinical signs in pigs of certain ages
Recombinant DNA, deletion-mutation, live-attenuated, and inactivated vaccines are available
What are the two important Equine herpesviruses?
Equine herpes virus 1 (EHV-1)
Equine herpes virus 4 (EHV-4)
Distribution of EHV-1
Endemic in horse populations around the world
Transmission of EHV-1
Inhalation of infected aerosols
Direct or indirect contact with nasal discharges
Aborted fetuses, placenta or placental fluids
Latency of EHV-1
Can reside in tissues of CNS (specifically the trigeminal ganglia) and lymph system (leukocytes or lymphocytes) without causing any clinical symptoms
When host is immunosuppressed; the virus is then reactivated, causing disease, or shedding of virus once again
T/F: cell-associated viremia protects EHV-1 from the immune system, allows spread into endothelial lining of blood vessels int he CNS and pregnant uterus
True
The principal route of EHV-1 infection is via the _______ tract
Respiratory
T/F: following infection of epithelial cells, EHV-1 infects endothelial cells of the lamina propria
True
Virus-infected _________cells and _ __________ subsequently appear in the drainage lymph nodes and are released into the circulation producing viremia
Mononuclear; T lymphocytes
T/F: Following infection of respiratory epithelium (EHV-1), latent infections are established in circulating T lymphocytes and trigeminal ganglionic neurons
True
Reactivation of BHV-1 results in shedding of virus from ______ epithelium and probably ______ infection
Nasal; uterine
Central lesion caused by EHV-1 is responsible for three types of conditions seen is an infection of endothelial cells. What does this lead to?
Vascular necrosis
Thrombus formation
Subsequent death to the tissues serviced by these blood vessels
Cell-associated viremia confers protection from the body’s immune defenses and allows the virus to spread to endothelial cells lining blood vessels in the CNS and pregnant uterus, resulting in ___ signs or ____.
CNS; abortion
Pathogenesis of EHV-1
Immunosuppression
EHV-1 Respiratory disease
Affects mostly younger horses
Rhinopneumonitis
EHV-1 Encephalomyelopathy (EHM, equine herpesvirus myeloencephalopathy) affects what group?
May affect horses of any age or breed
EHV-1 Reproductive form
Abortions may occur early in gestation, the majority occur in the last trimester
Repro efficiency is not compromised
Cases of abortion are usually sporadic
If large numbers of susceptible mares are exposed to the aborted conceptus, extensive outbreaks of abortion (abortion storms) occur
Natural immunity may last 2-3 years, which is why abortion storms tend to show after 3 year cycles
Equine viral Rhinophneumonitis
EHV-4 antigenically related to EHV-1
Transmission of Equine viral rhinopneumonitis
Most infections with EHV-4 are sporadic
Mostly observed in horses under 2 yo
EHV-4 often causes a lifelong latent infection, which can be reactivated
Droplet infection from infected horses and older horses in which inapparent viral shedding occurs
Pathogenesis of EHV-4
Causes less severe tissue destruction than EHV-1
Rarely causes abortion when it infects pregnant mares
Rarely results in viremia
Death is rare
Clinical signs for EHV-4
Infection results primarily in upper respiratory tract disease (rhinopharyngitis and tracheobronchitis)
Vaccination of EHV-1 and EHV-4
Ideally should prevent infection of suckling foals as well as latency of infection in pregnant mares
Live-attenuated and inactivated commercial EHV-1 vax are available, including combined products that include both EHV-1 and EHV-4
Immunity is short-lived
What does Canine herpesvirus 1 (CHV-1) cause?
Hemorrhagic disease of puppies (fading puppy syndrome)
Etiology of Hemorrhagic disease of puppies
Canine herpes virus 1, subfamily: Alphaherpesvirinae
Hosts of CHV-1
Dogs
Wild canids
Highly fatal
Generalized hemorrhagic disease of puppies
Transmission of CHV-1 in neonates
Contact with infected oral, nasal or vaginal secretions of dam Contact with secretions of litter mates In-utero transmission From passage through birth canal Contact with infected fomites (rare)
Transmission of CHV-1 in older dogs
Venereal transmission
Contact with saliva, nasal discharge, or urine of infected dogs or puppies
Pathogenesis of In utero CHV-1 infection in puppies
Abortion
Still birth
Infertility
If they survive, most pups develop systemic CHV-1 infections within 9 days from birth
Pathogenesis of systemic neonatal infection
Pups less than 1 week old are most susceptible to fatal generalized infection
Initial replication occurs in nasal epithelium, tonsils and pharynx
Mucosal invasion is followed by leukocyte (macrophage)-associated viremia
Virus replication in endothelial cells
Diffuse necrotizing vasculitis, multiple hemorrhagic necrosis in several organs
Thrombocytopenia, DIC
Pathogenesis of CNS infection of CHV-1
Meningoencephalitis commonly occurs in oro-nasally infected neonatal puppies.
Virus may travel up the nerve axons to CNS.
However, puppies die from systemic illness before neurologic signs are evident
What are the two main factors governing systemic neonatal infection?
Body temperature of puppies is critical
Maternal immunity
Why is the body temp of puppies critical when it comes to CHV-1?
Replicates at 33C - temp of the outer genital and upper respiratory tracts
Hypothalamic thermoregulatory centers of the pup are not fully operative until 2-3 weeks of age
Pup is critically dependent on ambient temp and maternal contact for the maintanence of it’s normal body temp
The more severe the hypothermia, the more severe and rapid is the course of the disease
Why is maternal immunity important?
Maternal antibodies provide protection.
Pups born from seronegative bitches are highly vulnerable to severe form of disease
Clinical signs of CHV-1 in puppies
Painful crying Abdominal pain Anorexia Dyspnea Passing soft, odorless greenish stool No elevation in body temp
Survivors develop persistent neurolgical signs, such as ataxia, blindness
CHV-1 Adult genital infection
Bitches:
Generally asymptomatic or limited to vaginal hyperemia
Vesicular vaginitis with discharges, vesicular lesions.
In-utero infection may result in abortion, stillbirth, mummified fetus, and/or infertility
Male:
Balanoposthitis
CHV-1 Adult respiratory infection
Older dogs:
Mild respiratory infection (rhinitis and pharyngitis)
Ocular infection from CHV-1
Conjunctivitis
CHV-1 Control
Reduce hypothermia by providing heated whelping boxes, or placing puppies under infrared lamp
Low prevalence of severe illness in pups and paucity of clinical signs in adult animals has resulted in lack of availability of vaccines
Feline herpesvirus 1 causes what?
Feline Rhinotracheitis
What are the two main causes of infectious respiratory disease of cats?
Feline herpes virus 1 Feline calicivirus (FCV) (family Caliciviridae)
Transmission of Feline herpesvirus 1
FHV-1 is shed primarily in ocular, nasal and oral secretions
Spread is largely by direct contact with an infected cat
Aerosol route in not considered important
Natural routes of infection are nasal, oral and conjunctiva
All recovered cats become latently infected carriers
Reactivation may cause viral shedding in organs all and conjunctival secretions
Pathogenesis of FHV-1
Replication takes place predominantly in the mucosa of the nasal septum, turbinates, nasopharynx and tonsils.
Viremia is rare, as virus replication is restricted to areas of low temperature, upper respiratory tract
Infection leads to areas of multifocal epithelial necrosis, inflammation and fibrinous exudation
Secondary bacterial infection can cause complications
Clinical signs of FHV-1
Kittens (up to 4 weeks): Severe upper respiratory disease Extensive rhinotracheitis Fatal bronchopneumonia may develop Conjunctivitis and ulcerative keratitis
Cats (6 months or older):
Mild or subclinical disease in older kittens
What are the clinical signs of FHV-1 in pregnant queens?
Abortion around the 6th week of pregnancy
No evidence that the virus crosses the placenta
May be due to severe systemic effects of illness, and not direct effect of virus
What are the 2 things that are common with feline rhinotracheitis?
Conjunctivitis with hyperemia and serous ocular discharge
Ulcerative keratitis
Are ulcers on the tongue common with feline calicivirus (FCV)infection?
Yes
Are oral ulcers common in cats with FHV-1 infections?
No, rare
T/F: you can have severe necrohemorrhagic rhinitis and multifocal necrohemorragic palatitis with feline rhinotracheitis
True
Vax of FHV-1
Three types of FHV-1 and FCV are available:
MLV (modified live virus) parenterally
MLV intranasal
Inactivated vaccine parenterally
What are the two avian diseases we are worried about in the herpesvirus world?
Infectious laryngotracheitis (Gallid herpesvirus 1) Marek's disease (Gallid herpesvirus 2)
Etiology of infectious laryngotracheitis (ILT)
Gallid herpesvirus 1
Hosts of ILT
Highly contagious infection of chickens
Transmission of ILT
Inhalation**
Droplets by conjunctiva
Occasionally by ingestion
Recovered and vax chickens can also serve as carriers of ILT and can shed the virus when they are subjected to stressful conditions
Transmission can occur through fomites such as contaminated litter, and/or farm workers
Mechanical transmission, especially through scavengers like vultures, crow, domestic dogs and wild animal that feed on improperly disposed dead birds
Pathogenesis of ILT
Severe laryngotracheitis in affected birds
Extensive diphtheritic membrane formation can form a second tube for the length of trachea, blocking the air passage. This can result in death from asphyxia
ILT virus can persist in the infected birds. The trigeminal ganglion is the target for ILT viral latency
T/F: with ILT, birds can have hemorrhagic tracheitis, necrotizing hemorrhagic tracheitis, and tracheal plugs
True
Severe form of ILT
Severe respiratory distress.
Head shaking with cough is characteristic.
Raised neck and extended head during inspiration - pump hardly respiration
Cough may result in expulsion of bloody mucous which may stain beak and neck feathers
Clinical signs of ILT
Strains of low virulence are associated with conjunctivitis, ocular discharge, swollen infraorbital and nasal sinuses, and decreased egg production.
The mild enzootic form in most common in modern poultry production, and the severe epizootic form in uncommon
Diagnosis of ILT
Necropsy findings: tracheal plug (diphtheria membrane)
Detection of typical intranuclear inclusions in respiratory tissues
Virus isolation: nasal mucosa
Virus grows well in CAM of embryonated eggs
Control of ILT
In an outbreak, complete depopulation (slaughter) of infected birds, and disinfection of infected premises
3 types of vaccines for ILT
- Chick embryo origin (CEO) - have the capability of reverting to virulence and causing full-blow ILT signs, induces better immunity.
- Tissue culture origin (TCO) - only given by eye drop and does not spread significantly or revert to virulence. Level of induced immunity is limited
- Pox-vectored recombinant vax
* These are applied via eye drop, or through mass vax by water or spray
Farm biosecturity of ILT
Implementation of farm biosecurity measures
What is Marek’s Disease?
Caused by Gallid herpesvirus 2
Important disease of poultry
Hosts of Marek’s disease
Chickens are the most important natural host
Turkeys, quails, pheasants are susceptible
Transmission of Marek’s disease
Highly contagious
Inhalation of infectious feather debris, chicken dander, or dust
Cell free viruses release from the feather follicles are highly infectious, but labile
Viruses in desquamated cells (dander) are less infectious, but can survive in poultry house dust or litter for several months
What are the 4 pathotypes of Gallid herpes virus 2?
Mild [mMDV]
Virulent [vMDV]
Very virulent [vvMDV]
Very virulent plus [vv+MDV]
Mild [mMdv]
Mostly associated with neural MD.
Disease is preventable with HVT (turkey herpesvirus vaccine)
Virulent [vMDV]
Associated with high incidence of neural and visceral lymphomas.
Disease is preventable with HVT
Very virulent [vvMDV]
Associated with high incidence of neural and visceral lymphomas
Viruses are oncogenic in HVT vaccinated chickens.
Disease preventable with bivalent vaccines
Very virulent plus [vv+MDV]
Associated with high incidence of neural and visceral lymphomas.
Viruses are oncogenic in chicken vaccinated with bivalent vaccines
Marek’s disease pathogenesis
Fully productive infection: occurs in feather follicle epithelium. Infected T cells appear to be the ‘Trojan horse’ by which MDV enters the feather follicle epithelium
Inhalation of virus -> initial round of replication in epithelial cells -> macrophage associated viremia -> virus is detectable in the spleen, thymus and the bursa of Fabricius -> productive restrictive infection: cytolytic replication primarily in B cells and later activated CD4+ T cells -> non-productive latent infection in CD4+ T cells -> non-productive neoplastic transformation: some latently infected CD4+ T cells
For MD, what is a fully productive infection?
Production of enveloped virions and cell death (lysis)
Occurs only in feather follicle epithelium.
Infected T cells appear to be the ‘Trojan horse’ by which MDV enters the feather-follicle epithelium
Productive-restrictive infection for MD
Production of naked virions (not infectious) and viral antigens
Cell death due to lysis
Occurs in B-cells and activated T cells (primarily CD4+ cells)
Profound immunosuppression
Non-productive infection of MD
Viral genome persists in T cells (primary CD4+)
No antigens expressed
Non-productive neoplastic transformation of MD
Some latently infected T cells undergo neoplastic transformation
A new antigen, MATSA (MD associated tumor specific antigen), appears in transformed T-cells
MD virus is slowly _____ and remain associated with cells. Cell-free infectious viruses are almost impossible to obtain, except in dander from _______ _________.
Cytopathic; feather follicles
Lesions in MD result from infiltration and in situ proliferation of transformed _ __________. Cell lysis also results in marked inflammatory response
T lymphocytes
Clinical features of MD
Neurolymphomatosis
Visceral lymphomatosis
Ocular lymphomatosis
Cutaneous lymphomatosis
Neurolymphomatosis
Enlargement of nerve trunks.
Nerves lose their striations
Edematous, grey, or yellowish in appearance.
Lameness Droopy wings Paresis of legs Limberneck Torticollis Incoordination
Visceral lymphomatosis
Diffuse or nodular lymphoid tumors may be seen in various organs, particularly the liver, spleen, gonads, heart, lung, kidney, muscle, and proventriculus.
The bursa is only rarely tumorous and more frequently is atrophic. The absence of burial tumors helps distinguish this disease from lymphoid leukosis
Ocular lymphomatosis
Grading of the iris (aka gray eye, cats eye, or pearl eye) of one or both eyes.
Interference with normal pupil are constriction and dilation.
Partial or total blindness
Cutaneous lymphomatosis
Plucking of feathers reveal nodular lesions on skin
Enlarged feather follicles (commonly termed skin leukosis)
Vaccination for MD
Most widely used consists of turkey herpesvirus (HVT)
Bivalent vax consisting of HVT and either the SB-1 or 301B/1 strains of Gallid herpesvirus 3 (serotype 2, avirulent strain)
Most protective commercial vax available appears to be CVI988/Rispens, an attenuated MD virus strain that is also commonly mixed with HVT at vaccination
General properties of the subfamily Betaherpesvirinae
Slow replication
Associated with chronic infections
Infected cells are often enlarged (cytomegaly)
Maintained in latent form in secretory glands (salivary glands) and lymphoreticular cells (macrophages, lymphocytes)
Often associated with continuous viral excretions
Etiology of Inclusion Body Rhinitis
Porcine herpesvirus 2 aka Porcine cytomegalovirus (PCVM) subfamily Betaherpesvirinae
Hosts of Inclusion Body Rhinitis
Pigs
Severe disease in piglets
Transmission of Inclusion Body Rhinitis
Primarily inhalation
Transplacental transmission
Pathogenesis of Inclusion Body Rhinitis
Widespread petechiae and edema
Most common in thoracic cavity and SQ tissues
Primary site of viral replication: nasal mucus glands, epithelial cells of upper respiratory tract
In some neonates, bone marrow damage and anemia
Still birth, mummification, neonatal death
Endothelial cell damage and necrosis: petechial hemorrhages and edema
With Inclusion Body Rhinitis, infected cells are enlarged and posses _______ inclusion bodies, especially in ______ glands. Hence, known as Inclusion Body Rhinitis
Intranuclear; nasal
Clinical signs of Inclusion Body Rhinitis
In suckling pigs <3wo, mucopurulent rhinitis
Infected neonatal piglets appear weak, anemic or stunted with edema around the throat and tarsal joints
Fetal mummification, stillbirths, neonatal deaths and failure of piglets to thrive have been associated with infection of naive, pregnant sows
Subclinical disease in older animals
Subfamily Gammaherpesvirinae general properties
Lymphotropic (replicate in B or T lymphocytes)
Slowly cytopathic for epithelial and fibroblastic cells, causing death without virion production
Some gammaherpesviruses are shed continuously from epithelial surfaces
Latency occurs in lymphoid tissues
Some members cause lymphoid tumors
Etiology of Malignant Catarrhal Fever (MCF) aka Bovine Malignant Catarrh
Viruses in subfamily Gammaherpesvirinae
At least 10 viruses have been recognized
Two most important MCF viruses are:
Alcephaline herpesvirus-1 (AHV-1) aka Wildebeest-associated MCF
Ovine herpesvirus-2 (OvHV-2) aka Sheep-associated MCF
Wildebeest-associated MCF [Alcephaline herpesvirus-1
AHV-1 is trasmitted to cattle from wildebeests.
Occurs in most African countries, where cattle commingle with infected normal wildebeest
AHV-1 does not cause any disease in the wildebeest
Epizootic and seasonal (during the wildebeest calving season)
Sheep-associated MCF [ovine herpesvirus-2 (OvHV-2)]
Worldwide
Transmitted from sheep to cattle
Goats also can act as a source of infection to cattle
Occurs year-round in cattle, with moderate increase during lambing season
Usually sporadic, occasionally outbreaks
T/F: In Africa, MCF is predominantly found where cattle are in close contact with blue-or black wildebeest, while outside Africa, it is usually associated with contact between sheep and susceptible species
True
Transmission of wildebeest-associated MCF
Between wildebeest: horizontal and occasionally intrauterine transmission in wildebeest. Inapparent infection.
From wildebeest to cattle:
AHV-1 is present in nasal and ocular secretions of young wildebeest in a cell-free state.
Ingestion of pasture contaminated with nasal or ocular secretions from young wildebeests.
Direct or close contact, inhalation of aerosol with young wildebeest
Direct or close contact with wildebeest during calving
Virus in cell-associated form in adult wildebeest, so rarely transmitted from adults
Transmission of sheep-associated MCF
Between sheep:
Respiratory
Transplacental rare
Contact with nasal secretions
Sheep to cattle:
Not known
Presumably by inhalation or ingestion
Transmission of MCF between wildebeest and sheep
Inapparent infection in wildebeest and sheep.
Virus transmitted from wildebeest-to-wildebeest and sheep-to-sheep
Cattle’s role in MCF
Cattle are dead-end hosts. No evidence from transmission of virus from cattle-to-cattle.
Cattle have cell-associated virus, but not cell-free virus, in secretions.
This may explain the noncontagious nature of MCF when contact occurs with MCF affected cattle
Pathogenesis of MCF
Infection followed by cell-associated viremia.
Lymphoid proliferation and infiltration
Necrotizing vasculitits
Vascular lesions, gross lesions such as epithelial erosions and keratoconjunctivitis
Clinical signs of MCF
Peracute form: sudden death
Head and eye form: majority of cattle cases
Alimentary/intestinal form: initially like head and eye form, but death occurs from severe diarrhea. Diarrhea is rarely observed in wildebeest derived MCF, but is more common in sheep associated MCF
Mild form: inoculated animals; recovery expected
Peracute form of MCF
Sudden
Characteristic clinical signs of head and eye form may not appear
High fever
Acute gastroenteritis
Head and eye form of MCF
Early stages Reddened eyelids Bilateral corneal opacity Crusty muzzle, nares Nasal discharge Salivation Erosions of the tongue, hard palate, and buccal papillae (along with necrosis)
What is zebra striping?
Necropsy finding of MCF in the bovine colon.
Severe longitudinal linear congestion of the mucosa
Control of MCF
Separation of cattle from wildebeest and sheep
Incidence too low to justify development of a vaccine
Etiology of African Swine Fever (ASF)
Sole member of family Asfarviridae
Only known DNA arbovirus
Hosts of ASF
All breeds and types of domestic pigs and European wild boar
Inapparent infection in warthogs, bush pigs and giant forest hogs, which act as reservoirs
T/F: ASF is an OIE List A Disease
True
Geographical distribution of ASF
Endemic:
Most of sub-Saharan Africa
Island of Sardinia (Italy)
Recent outbreaks:
Eastern Europe and Russia
The virus has continued to spread within the Russian Federation
ASF Virus Stability
Virus survive at least 30 days in pens Very resistant to s wide range of pH Survive in chilled carcass Highly resistant to putrefaction Remains viable for long periods in blood, feces and tissues Can multiply in vectors
Transmission of ASF
Vector: soft ticks (Ornithodorus sp, specifically O moubata in Africa)
Ornithodorus sp are biological vectors of the virus
Virus replicates in the tick, resulting in trans-stadial, transovarial, and sexual transmission (male-to-female)
Infected ticks may live for several years and capable of transmitting virus to pigs during each blood meal
ASF reservoirs (Sylvatic cycle)
Warthog
Giant Forest Hog
Bush Pig
Cycles that exist in the transmission of ASF
Domestic cycle between pigs
Enter ticks and begins the sylvatic cycle
Adult warthogs:
No viremia, virus in various lymphoid tissues
Juvenile warthogs:
Significant viremia
Sylvatic cycle of ASF
Between warthogs and soft ticks
ASF maintained because of soft ticks and asymptomatic infection in wild pigs
After primary infection, young wild pigs develop a viremia with high enough virus titers to infect ticks feeding on them
Older wild pigs are persistently infected, but rarely develop viremia
Domestic cycle of ASF
Meat products -> waste food -> fomites -> direct contact via secretions and blood loss
Primary outbreaks in domestic swine:
Bite of infected tick
Direct contact with infected animal
Indirect contact on fomites
Virus spreads to new areas when pigs are fed uncooked scraps that contain infected pork
Aerosol spread
Mechanical transmission through biting flies
All body fluids and tissues contain large amounts of infectious virus
Pigs that survive infection may become carriers and shed virus in secretions and excretions
Pathogenesis of ASF
The effects of ASF virus are primarily hemorrhages and apoptosis
There is leukopenia, thrombocytopenia
Apoptosis of host cells with ASF
P54 protein (encoded by virus) directly induces apoptosis of host cells
ASF infected macrophages release cytokines and apoptotic mediators
Apoptosis of both lymphocytes and mononuclear phagocytic cells
Mechanisms related to hemorrhages of ASF
Vascular damage from degeneration of vascular endothelium
DIC
Infection and necrosis of megakaryocytes
Activation and extensive destruction of monocytes and macrophages
Thrombocytopenia and coagulation defects lead to:
Edema, infarction, exudation and hemorrhages in many organs and tissues
Peracute clinical signs of ASF
Pigs may die suddenly
Acute form clinical signs of ASF
High fever
Cyanotic skin blotching on the ears, tail, lower legs or hams**
Respiratory distress
Diarrhea: initially mucoid and later may become bloody
Abortion: sometimes the first event seen in an outbreak
Death
T/F: In white-skinned pigs with suspected ASF, the ears, tail, legs and underside appear deeply flushed and may develop a bluish tinge or cyanosis
True
Chronic form clinical signs of ASF
Emancipation and stunting
Swollen joints
Ulcers and reddened or raised necrotic skin foci
Pneumonia
Cutaneous lesions
Fibrinous pericarditis and myocardial hemorrhage
What happens to the spleen of pigs with ASF
Becomes large and friable or blackberry jam spleen
Immunity to ASF
Although infected pigs produce virus-specific antibodies, sera from infected pigs do not neutralize the virus, hence humoral immune response does not seem to have substantial protective value
Therefore, attempts to develop a vaccine have so far been unsuccessful
To prevent ASF
Pig farmers and field personnel should be aware of ASF, able to recognize ASF and know what to do if they suspect ASF.
Pigs should be kept in well-constructed pig sties under hygienic conditions with controlled entry to the piggery.
Movement of pigs inside the country and especially across international borders should be controlled
Pigs shouldn’t be fed swill that might contain remains of pigs. To ensure safety, swill should be boiled for 30 minutes and cooled before feeding
During ASF outbreaks
IMMEDIATELY NOTIFY AUTHORITIES
Infected and suspected infected farms must be placed in quarantine
No movement of pigs or any products of pig origin should be allowed
All infected an in-contact pigs must be slaughtered
Carcasses must be burnt or buried deeply on site
Vehicles should be disinfected on entering and leaving farms
Personnel should ensure that shoes, clothes and equipment are disinfected between farms
Family Parvoviridae general properties
Viruses are very stable
Disinfection of contaminated premises is difficult
Replication of Parvoviridae
Occurs in the nucleus of dividing cells
Infection leads to large intranuclear inclusion bodies
Genus parvovirus
Virus replication occurs only in cells that pass through mitotic S phase (actively dividing cells)
Cannot replicate in stationary cells, as rely on enzymes of actively dividing cells (mitosis)
Human parvovirus B19
Different from parvovirus seen in dogs and cats. No evidence of transmission of B19 to humans from dogs or cats, or vice versa
Feline panleukopenia is aka what?
Feline distemper
Feline infectious enteritis
Etiology of feline panleukopenia
Feline parvovirus
Hosts of feline panleukopenia
Highly contagious, often fatal disease of cats
Severe in mittens
Epidemiology of FPV
The virus is ubiquitous because of its contagious nature and capacity for persistence in the environment
Virtually all cats are exposed and infected within first year of life
Unvaccinated kittens that acquire maternal antibodies are protected up to 3 months of age
Most infections are subclinical, as much as 75% of unvaccinated healthy cats have demonstrable antibody titers by 1 year of age
Can cats shed FPV in their urine or feces? If so,for how long?
Yes, 6 weeks after recovery
T/F: FPV is maintained in population by prolonged viral shedding rather than by environmental persistence
False, other way around
Owners losing a kitten to FPV should/should not introduce a new kitten into the household without having it vaccinated
Should NOT
Transmission of FPV
Cats are infected oro-nasally by exposure to infected animals, their feces, secretions or contaminated fomites
In-utero transmission occurs
Mechanical transmission by flies
What are the hallmarks of Panleukopenia
The more severe the leukopenia, the poorer the prognosis
The characteristic profound leukopenia involves destruction of all WBC elements, including lymphocytes, neutrophils, monocytes and platelets
Thrombocytopenia may accompany leukopenia
FPV enteritis
Virus selectively damages replicating cells deep in the crypts of the intestinal mucosa.
Loss of cells from tip of villus continues as a normal process. Since virus replicates and destroys cells of crypts, there is no replacement of the lost absorptive cells at tips of the villi with cells of the crypts
Resulting in shortening of intestinal villi, marked villus blunting and fusion, malabsorption and diarrhea
FPV in-utero infections
Early in-utero in pregnant queens can result in:
Early fetal death and resorption with fertility
Abortions
Birth of mummified fetuses
Infection closer to end of gestation:
Birth of live kittens with varying degree of damage to the late-developing neural tissues
Variable effects on kittens from the same litter
FPV CNS infections
CNS, optic nerve and retina are susceptible to damage by FPV during prenatal or early neonatal development
Of neurological lesions, cerebellum damage has been most commonly reported
Cerebellar hypoplasia is usually observed in fetuses infected during the last 2 weeks of pregnancy and the first two weeks of life
FPV cerebellar hypoplasia
Lysis of mitotic cells of the external germinal layer
Impaired cerebellar development
T/F: Ataxia is common in kittens with FPV
True
FPV and DIC
Kittens with FPV infection are susceptible to secondary infections
Gram- endotoxemia, with or without bacteremia is common sequelae of systemic FPV infection
Endotoxin (LPS) induces expression of tissue factor [factor III] on endothelial cells
Tissue factor is a potent activator of coagulation, resulting in DIC, followed by hemorrhages
Clinical signs of FPV
Most common in kittens Fever Depression Anorexia Rough coat Repeated vomiting Profuse, persistent and frequently bloody diarrhea Severe dehydration Hypothermia Sudden death from complications of secondary infection, dehydration and DIC
What are the consequences and clinical manifestations of FPV affected intestinal crypt epithelium?
Villous collapse, enteritis
Diarrhea
What are the consequences and clinical manifestations of FPV infected lymph nodes, thymus?
Germinal center depletion, apoptosis of lymphocytes, thymic atrophy
Lymphopenia
What are the consequences and clinical manifestations of FPV infected bone marrow?
Stem cell depletion
Neutropenia -> thrombocytopenia and anemia
What are the consequences and clinical manifestations of all fetus FPV infected cells
Fetal death
Loss of pregnancy
What are the consequences and clinical manifestations of FPV infected developing cerebellum cells?
Cerebellar hypoplasia
Cerebellar ataxia
T/F: Queens infected or vaccinated during pregnancy may show infertility or abortion of dead or mummified fetuses.
True
How old are kittens when cerebellar hypoplasia and ataxic signs appear?
3-4 weeks
_____ degeneration is seen in kittens infected with FPV
Retinal
Diagnosis of FPV
Hematology: leukopenia, neutropenia more consistent than lymphopenia - total WBC counts <2000 cells/uL are associated with a poorer prognosis
Fecal viral antigen testing using immunochromatographic test kit or ELISA: results may remain positive up to 2 weeks following MLV vaccination
Serological testing for diagnosis of FPV
Single sample antibody titers do not distinguish between active or past infections/exposure to virulent or vaccine strains
Paired serum samples, the 1st ASAP during illness, and second 2 weeks after.
A fourfold rise in titer is considered indicative of acute infection
Virus neutralization test is commonly used
Treatment of FPV
Good nursing care, fluid therapy, withholding in early stages to lessen volition and slow down mitotic activity of cells
Broad spectrum antibiotics to prevent secondary bacterial infection
Control of FPV
Large catteries: strict hygiene and quarantine of incoming cats
Disinfection: inactivated by bleach [6% sodium hypochlorite], 4% formaldehyde and 1% glutaraldehyde in 10 minutes at room temp
Vaccination of FPV
Attenuated (modified) live vaccines (MLV)
MLV should not be administered to: Pregnant cats Immunosuppressed cats Sick cats Kittens less than 4 weeks old
Is canine parvovirus 1 an important virus in dogs?
Nope.
Mild to inapparent illness (diarrhea) in dogs, especially in young pups less than 8 weeks old.
Name that virus: one of the most common infectious diseases of dogs. Has three antigenic variants: CPV-2a, CPV-2b, CPV-2c
Canine parvovirus 2 (CPV-2)
Distribution of CPV-2
North America, CPV-2b and CPV-2c are more common
Epidemiology of CPV-2
Virus is highly contagious and very stable in the environment
Resistant to many common detergents and disinfectants
Infectious CPV can persist indoors at room temp for at least 2 months
Transmission of CPV-2
Oro-nasal exposure to contaminated feces
In-utero infection
Contact with virus-contaminated fomites (environment, personnel, equipment)
Pathogenesis and clinical findings of CPV-2
Enteritis
Myocarditis
Panleukopenia
Similar to FPV
Enteritis with CPV-2
CPV-2 infects the germinal epithelium of the intestinal crypts, causing destruction and collapse (and necrosis) of the epithelium. No replacement of cells lost from tip of villus. Villi shortened and hemorrhagic diarrhea
Hemorrhagic enteritis
Ballooned small intestine
Ingesta visible through small intestine wall
Myocarditis with CPV-2
Develops from infection in-utero or from pups <6 wo
Myocardial necrosis with acute cardiopulmonary failure
Sudden death, or die after short period of clinical signs
Diagnosis of CPV-2
Serology (antibody detection) is not best method to test CPV, because most dogs are vaccinated, or have been previously exposed
What test is done in clinic that can test for parvo?
SNAP Parvo Test
Vax for CPV
Because of potential damage by CPV to myocardial or cerebellar cells, inactivated rather than modified-live vaccines are indicated in pregnant dogs or colostrum-deprived puppies vaccinated before 6-7 wo
Use of oseltamivir (tamiflu) in the treatment of canine parvoviral enteritis
MOA no clear, as parvovirus does not use neuraminidase in its replication
Speculation is that neuraminidase is an important enzyme used by pathogenic bacteria invading through the protective mucous barrier of the GI tract, and by this process indirectly facilitate CPV infection. Tamiflu may act on these bacterial neuraminidase
Porcine parvovirus
Is an infectious cause of reproductive failure in swine throughout the world
Some manifestations of the disease are described by the acronym SMEDI (stillbirth, mummification, embryonic death, infertility)
In most herds, a large proportion of gilts are infected naturally before they conceive, and hence are immune
Transmission of porcine parvovirus
Oronasal in the non-immune pregnant sow followed by transplacental transmission.
Venereal transmission is possible
Pathogenesis of porcine parvovirus
Organs also infection of the nonimmune pregnant dam followed by viremia
After maternal infection of the virus to reach the fetus
Transplacental infection of porcine parvovirus
Death at different stages of pregnancy is typical of PPV infections
What is the hallmark of PPV?
Increase in mummified fetuses after a normal gestation period
Are abortions common in PPV
Uncommon
What Times of infection is critical for PPV
Embryo/fetus (<30 days): dies and resorbed. Dams may return to estrus Early fetus (30-70 days): fetuses die and become relatively dehydrated (mummified) Late fetus (>70 days to term): frequently develop lesions, but also mount an immune response and usually survival in-utero
T/F: with PPV, boars, sows and gilts have mostly inapparent or subclinical infections
True
Diagnosis for PPV
Serologic tests are of limited value, because the virus is so widespread in swine, and vaccination may interfere
Immunity to PPV
Unlike most parvoviruses, PPV can cause persistent infection with periodical shedding of virus
Vaccination/immunization to PPV
Many inactivated and live vaccines available to prevent PPV
Best way: vax all susceptible breeding stock twice, 2 weeks apart, several weeks before breeding
Alternatively, gilts can be naturally infected several weeks before breeding, by mingling with older breeding stock that may be shedding the virus
Can papillomaviruses transform cultured cells?
Yes
What do papillomaviruses produce on the skin and mucous membranes of most animal species?
Warts or papilloma
I hope you got that one!
The warts from papillomavirus are ______ ______ are hyperplastic epithelial outgrowths that generally regress ________
Benign neoplasms; spontaneously
T/F: Papillomaviruses are not species and site specific
False, they are specific
T/F: serologic cross-reactivity has not been detected among papillomaviruses of different species
True
Can the warts of papillomavirus progress to malignancy?
Yes. This is a property of specific virus strains i.e. HPV causing cervical carcinoma in women
Replication of papillomaviridae
Replication of papillomaviruses is linked intimately to the growth and differentiation of cells in stratified epithelium of the skin and some mucous membranes
The story of oncogenic papillomaviruses
In benign warts, the papillomavirus DNA is episomal, meaning it isn’t out integrated into the host-cell DNA and persists as an autonomously replicating episome.
In papillomavirus-induced malignant cancers the viral DNA integrated into that of the host. Thus, integration probably is necessary for Malignant transformation
Host of Bovine papillomatosis
Cattle
Warts are more commonly seen in cattle than in any other domestic animals
Natural bovine papillomavirus infection of horses (WHAT????) may occur after exposure of the horses to cattle
Transmission of bovine papillomavirous
Between animals by contaminated fomites, such as milking equipment, halters, nose leads, grooming and earmarking equipment
Sexual transmission of venereal warts in cattle
Fibropapilloma is mostly caused by what? What is it?
Bovine papillomavirus types 1, 2, and 5
Papilloma have a fibrous core covered to a variable depth with stratified squamous epithelium, the outer layers of which are hyperkeratinized
Lesions vary from small firm nodules to large cauliflower-like growths
Grayish to black in color and rough and spiny to the touch
Where are fibropapillomas common?
Udder and teats
Head
Neck
Shoulders
May also occur in the omasum, vagina, penis and anus
Cutaneous papillomas are caused by what and what are they?
Bovine papillomavirus type 3
Lesions lack a fibrous core
Are usually flat with a broad base, unlike the more usual fibropapillomas that protrude and are often pedunculated
What is the relationship between Bracken Fern and Bovine Papillomavirus?
Bovine papillomavirus 4 can cause transient papilloma in the alimentary tract. Ingestion of the bracken fern can result in transition to invasive carcinoma of the alimentary tract
In cattle that eat broken fern, papillomavirus types 1 and 2 may also contribute to the syndrome of “enzootic hematuria” that is characterized by hematuria and/or urinary bladder cancer
Treatment of bovine papillomatosis
Surgical excision, or cryosurgery with liquid nitrogen
Topical agents, podophyllin and undiluted medical grade DMSO (dimethylsulfoxide)
Bovine interferon-alpha
Wart vaccine (yes, it’s a thing apparently)
Canine oral papillomatosis
Contagious, self-limiting disease affecting oral cavity of dogs
The warts usually begin on the lips, and can spread to the buccal mucosa, tongue, palate and pharynx. Later may become roughened and cauliflower-like. Do not extend below epiglottis or into esophagus
Lesions typically regress spontaneously
Progression to squamous cell carcinoma occurs very rarely
Clinical signs of canine oral papillomatosis
Halitosis (bad breath), hemorrhage, ptyalism (hypersalivation), discomfort
Numerous warts may interfere with mastication and deglutition
Warts may regress, or secondary bacterial infection and ulceration may occur
Ocular warts: conjunctiva, cornea, eyelid margins
Recovered dogs are refractory to reinfection
Treatment of canine oral papillomatosis
Surgical excision, cryosurgery, electrosurgery
Auto genius vaccines
Equine sarcoids
Commonly occur in horses, donkeys and mules between 1-6 yo. Most common neoplasm of horses**
They are locally invasive benign fibroblastic skin tumors
Associated with bovine papillomaviruses 1 and 2
Do not metastasize. They may persist for life. Are locally invasive. Recur after surgical removal
Equine sarcoids transmission
Mode of transmission has not been confirmed
Flies act as vectors maybe?
Fomites, transmitted via stable management practices
What do equine sarcoids look like?
Lesions commonly occur in traumatized areas
Single or multiple
Growths may reach size of man’s fist, bulge under skin
May become ulcerated
Treatment of equine sarcoids
Cryotherapy
Surgical or laser excision
Local immune modulation
Local radiotherapy
Morphology of Adenoviridae
Non-enveloped, precisely hexagonal in outline
12 vertex penton capsomers each with a fiber protrude from the surface of capsid
Genome and replication of Adenoviridae
Intranuclear inclusion bodies are formed, containing large numbers of virions, often in para-crystalline arrays
Adenoviridae general properties
Agglutinate RBCs. Hemagglutination occurring when the tips of penton fibers bind to surface of receptors on RBCs.
Some viruses are oncogenic in lab animals
Relatively stable in the environment, but are inactivated easily by common disinfectants
Most have narrow host ranges
Pathogenesis of adenoviruses
Cause acute respiratory or gastroenteric disease of varying severity
Mostly subclincal infections
Cause immunosuppression
Long periods of latency of adenoviruses
Viruses persist in lymphoid and other tissues, such as tonsil, adenoids, and Peyer’s patches
Reactivated in immunocompromised animals
Can be highly pathogenic in immunodeficient animals
Oncogenesis of adenoviruses
Under specialized conditions, some have been shown to be oncogenic
What are the two most important genera of adenoviruses?
Mastadenovirus: mammalian adenoviruses. A single penton fiber projects from each vertex
Aviadenovius: Avian adenoviruses. Each penton fiber is bifurcated, appear as two fibers extending from each penton base
Etiology of infectious canine hepatitis (ICH, Rubarth’s Disease)
Canine adenovirus-1 (CAV-1)
Transmission of CAV-1
Acute infection: found in all secretions and excretions
Afterwards, virus shed in urine for at least 6-9 months
Route: oronasal transmission Contact with: Secretions/excretions of infected dog Contaminated fomites Ectoparasites can harbor CAV-1
Sites of ICH virus replication
Macrophages Kupffer cells Hepatocytes Vascular endothelium of different organs including CNS Parenchyma cells of organs and tissues
Liver, kidneys, spleen and lungs are the main target organs!
Pathogenesis of ICH
At time of infection, dogs already with sufficient antibody titers (>500) show little clinical evidence of disease In acute cases, sufficient antibody response by day 7 post-infection [>500 antibody response by day 7 PI] clears virus from blood and liver and restricts hepatic damage Persistently low antibody titer (>4) will lead to widespread centrilobular to panlobular hepatic necrosis Partial immunity (antibody titer >16, but <500) may result in chronic active hepatitis and hepatic fibrosis
What happens in chronic cases of ICH?
Cirrhosis
What happens to the kidneys during ICH?
Acute infection - glomerulonephritis
Chronic kidney lesions may result from immune-complex reactions after recovery from acute or subclinical disease
Corneal edema with ICH
Blue eye
Occurs in about 20% of natural infections
Less than1% of dogs after S/C MLV-CAV-1 vax
Seen in dogs during recovery or chronic cases
How does corneal edema develop?
CAV-1 antibody production increases, and formation of viral-antibody immune complexes
This results in complement activation, neutrophil chemotaxis
Cause extensive damage to corneal endothelium
Disruption of intact corneal endothelium allows aqueous to enter the cornea
Accumulation of edematous fluid within corneal stroma results in corneal edema
Complications from ICH
DIC: Results from:
Damage to endothelium
Inability of diseased liver to remove activated clotting factors
Bacterial pyelonephritis resulting from renal damage
ICH clinical signs
Most frequent in dogs less than 1 yo
Concurrent parvovirus or distemper infection worsens the prognosis
Unvaccinated dogs of all ages are susceptible
Most infections are asymptomatic
Signs vary from a slight fever to death
Peracute cases of ICH
Severely infected dogs become moribund and die within few hours after onset of clinical signs
Acute cases of ICH
Fever of >104F (40C), depression, and anorexia
Vomiting
Occasionally abdominal pain, tenderness and hepatomegaly
Intense hyperemia or petechiae hemorrhages of the oral mucosa
Pale mucous membrane, jaundice
Enlarged tonsils, swollen lymph nodes
Subcutaneous edema of the head, neck and trunk
CNV involvement is unusual and is typically the result of vascular injury
Icterus is uncommon in early acute phase of ICH
Corneal edema and anterior uveitis occur when clinical recovery begins
Necropsy and histopathology findings of ICH
Paint-brush hemorrhages on the gastric serosa, lymph nodes, thymus, pancreas and subcutaneous tissues
Centrilobular necrosis in liver, with neutrophilic and monocytic infiltration, and hepatocellular intranuclear inclusions
Grayish white foci may be seen in the kidney cortex of recovered dogs or dogs with chronic disease
Diagnosis of ICH
Biochemistry and hematology:
Leukopenia persists throughout febrile period
Increased ALT and AST due to hepatic injury
Proteinuria
Prolonged prothrombin time, thrombocytopenia
Virus isolation: URINE, blood, tissue homogenates, etc
Treatment of ICH
Symptomatic and supportive. The goals of therapy are to limit secondary bacterial invasion, support fluid balance, and control hemorrhagic tendencies.
Immunity to ICH
Recovered animals are immune to systemic form of disease
Maternal antibodies interferes with active immunization until puppies are 9-12 wo
Attenuated CAV-1 live vaccines have produced transient unilateral or bilateral opacities of the cornea. Vaccine virus can cause mild subclinical interstitial nephritis, and may be shed in urine. Discounted in many countries.
CAV-2 attenuated live virus strains provide cross-protection against CAV-1. CAV-2 attenuated vaccines are preferentially used because they have very little tendency to produce corneal opacities or uveitis, and the virus is not shed in urine
Canine infectious tracheobronchitis (ITB, kennel cough) is what and what is the etiology?
Self-limiting upper respiratory disease of dogs
Multiple things can cause kennel cough. CAV-2 and Bordetella bronchiseptica (primary pathogen) are most prevalent
Transmission of ITB
Highly contagious via aerosolized droplets
Stress, unfavorable conditions increases severity of disease
Signs of uncomplicated ITB
Prominent sign is paroxysms of harsh, dry coughing, followed by etching and gagging.
Coughing causes a high pitched “honking” sound
Rhinitis, serous nasal discharges, sometimes conjunctivits
Signs of “complicated” ITB
Severe pneumonia or bronchopneumonia
Life threatening
Treatment of ITB
Antitussives when used in conjunction with broncodilators
Immunity to ITB
Modified-live virus vaccines against distemper, parainfluenza, and CAV-2, which also provides protection against CAV-1
Equine adenovirus
EAV-1 and EAV-2
Most are asymptomatic or present as mild upper or lower respiratory tract diseases
EAV-1 is associated with severe respiratory disease in Severe Combined Immunodeficiency (SCID) foals
As maternal antibody wanes, these foals become susceptible to adenovirus infection
Infection is progressive, and these foals invariably die with 3 months
Clinical signs of SCID in foals
Severe bronchiolitis and pneumonia. Respiratory distress and related signs
Avian adenoviruses in chickens
Inclusion body hepatitis
Egg drop syndrome ‘76
Avian adenovirus of ducks
Hepatitis (rare)
Avian adenoviruses of quail
Bronchitis
Avian adenovirus of turkeys
Hemorrhagic enteritis
Egg drop syndrome
Avian adenovirus of pheasants
Marble spleen disease
