Exam 2 Flashcards
Indicate whether most enteric viruses are enveloped or not, and describe why this is important.
- Most are not enveloped
- Helps stability in environment
Be able to outline the common pathogenesis for enteric viral infections as it relates to the intestinal mucosa architecture, segment of gut affected and clinical signs.
- Villous blunting (atrophy) = malabsorption & osmotic D
- Cl- secretion = water drawn to lumen = secretory D
- Inflammation = vascular permeability = loose tight junctions = exudative D
List the common features of enteric viruses with regards to transmission, incubation period, age of most susceptibility, host specificity.
- Fecal-oral transmission
- Short incubation period
- Severe disease in young animals
- Most are host species specific
- Most cause localized, transient infections
Describe which factors influence the severity of disease for enteric viral infections
- Dose of virus
- Host nutrition / health
- Underlying / concurrent infections
- Maternal Ab or vaccination
- Genetics of virus & host
Explain why it is important to provide non-oral fluid replacement in cases of rotavirus/coronavirus enteritis.
These viruses cause villus atrophy/blunting which results in decreased ability to absorb water and nutrients. If you give oral fluids, those fluids will not be absorbed in the intestine or at all.
Rotavirus: who does is affect? diagnosis? Pathogenesis? Treatment? Prevention?
- Species specific for cows, pigs, goats, horses, dogs, & humans
- non-enveloped & stable
- Results in acute white/yellow mucoid D (no blood) in baby animals (scours)
- Lasts 8-10 days
- Diagnosis: PCR/ELISA
- Pathogenesis: infects mature epithelial cells at villous tips in small intestine -> enterocyte damage = malabsorptive D & NSP4 enterotoxin -> secrete Cl- = secretory D
- Treatment: self-limiting, provide fluids & limit food
- Prevention: Vx dam prior to birthing, manage quality of housing, stress, nutrition
Coronavirus: enveloped or not? Pathogenesis?
- Enveloped but relatively stable
- Pathogenesis: infects mature epithelial cells at villous tips in small intestine -> enterocyte damage = malabsorptive D & enterotoxin -> secrete Cl- = secretory D
- Can also go to colon
2 Coronaviruses in Pigs
Transmissible Gastroenteritis (TGE) in pigs
- Highly contagious, localized enteric infection
- Incubation period 18-72 hrs - Naïve herds (never exposed to virus)
- All ages affected, mortality in young
- profuse diarrhea and some vomiting
- starts when maternal Abs waning
- Pathogenesis: same as any coronavirus
Porcine epidemic diarrhea virus (PED)
- Pathogenesis: same as any coronavirus
- New to US
Bovine Coronavirus 3 clinical presentations
- Calf diarrhea (similar to endemic TGE)
- Winter dysentery of adult dairy cattle: Sporadic acute enteric disease, diarrhea with blood, low mortality
- Respiratory disease
Equine Coronavirus; who does it affect? shedding? clinical signs? diagnostics? pathogenesis? treatment?
- usually affects adult horses
- Incubation period 48-72 hrs with peak viral shedding 3-4 days AFTER clinical signs
- Shedding is usually for 3-25 days, but up to 99 days
- Clinical signs: anorexia, lethargy, fever, mild colic, maybe Ds, neuro symptoms
- Diagnostics: CBC/Chem shows leukopenia & hypoalbuminemia
- Pathogenesis: Overgrowth of urease-producing bacteria or increase in ammonia absorption through disrupted small intestinal mucosa = hyperammonemia & associated encephalopathy
- Death unusual
- Treatment: fluid therapy and NSAIDS
Feline Enteric Corona Virus
- Common
- Subclinical or mild D
- Can mutate to feline infectious peritonitis (FIP)
Feline infectious Peritonitis (FIP) clinical signs, prevention, wet form, dry form
- Mutation from FECV or FIPV
- Usually < 1yo from multi-cat household
Clinical signs:
- fever, weight loss, anorexia
Prevention
- FIP vx is not effective
Effusive or wet form of FIP
- 75% of cases
- Inflammation of the serosal surfaces of the abdomen and/or thorax
- Accumulation of proteinaceous fluid in the body cavities
- Often leads to apparent abdominal distention, respiratory distress (due to pleural effusion)
Non effusive or dry FIP
- Pyogranulomatous inflammation following vessels of parenchymal organs
- kidneys, lymph nodes, liver, pancreas, CNS, uveal tract of the eye
- Effusion absent or minimal
Describe the importance in an individual cat’s immune response (humeral and CMI) in the development of disease with FIP infection.
- FIPV infection -> strong CMI (cell mediated) -> no disease
- FIPV infection -> strong Ab & weak CMI -> wet FIP
- FIPV infection -> weak Ab & moderate CMI -> dry FIP
Indicate the pathological cause for body cavity effusion in feline infectious peritonitis virus infection.
Kidneys and other organs are affected by pyogranulomatous vasculitis -> increases intravascular pressure -> leakage of high protein fluid
Describe the utilities of serology and PCR as diagnostic tests for feline infectious peritonitis virus infection and indicate the gold-standard for FIP diagnosis. Explain why it is difficult to diagnose FIP in a living patient, and what findings support a diagnosis.
- no single antemortem test available to diagnose FIP so combine serolgy & symptoms to presume diagnosis
definitive diagnosis:
- combine biopsy of grnauloma & immunohistochemistry
Parvovirus Pathogenesis & Clinical Findings
Pathogenesis
- Oronasal exposure -> entry & replication in GI lymph tissue -> moves to systemic lymph tissue -> systemic viremia -> Replication and necrosis of intestinal crypt epithelium, bone marrow, lymphoid tissue
Clinical Findings
- Fever, bloody osmotic D, & loss of immune cells
Explain how incorrect timing/frequency of parvovirus vaccination can lead to a lack of protection.
- If given too early, maternal Ab block pup from making own Abs
- If given too late, no maternal Ab and no own Ab = high exposure
- Should vaccinate multiple times while young to hopefully land in perfect window
Explain how mitotically active cells are important in the viral lifecycle and clinical pathogenesis of parvoviral enteritis
- Small DNA virus that does not carry DNA polymerase genes
- Uses cellular DNA polymerase
- Needs mitotically active cells to have plenty polymerase
- Crypt epithelium, lymph tissue, cerebellum (cat), heart (dog)
Parvovirus Treatment, Diagnosis, Prevention
Treatment
- Aggressive supportive care to counteract diarrhea & immunosuppression
- Antibiotics for secondary bacterial infections
Diagnosis
- Rapid antigen ELISA detects virus in feces (retest if negative because intermittent shedding)
- If fatal histologic lesions and intranuclear inclusions are diagnostic
Prevention
- Inactivated and attenuated (modified live) vaccines are available and effective
- Fecal shedding from vaccinated (MLVs) dogs can immunize other dogs
- DO NOT vaccinate pregnant or very young animals with MLV - potential for myocardial infections and cerebellar disease
Parvoviral Myocardial Disease in Dogs
- Was common when disease first emerged
- pups born w/out maternal Ab and susceptible to infection at a very early age
- Pups infected while myocardium still developing and susceptible to infection = acute heart failure and sudden death
- now pups usually not susceptible at young age or infected when older and myocardium no longer in active development
Parvoviral Cerebellar Disease in Cats
- Infection during late gestation/early neonatal period
- Virus has tropism for cells in the cerebellum
- cerebellar hypoplasia most commonly
- Ataxia, incoordination, tremors, broad-based stance with hypermetric movements
Canine Adenovirus
- Non-enveloped, stable DNA virus
- Seldom seen anymore due to highly effective vaccination
- <1yrs or unvaccinated dogs
- Clinically-asymptomatic to fatal
- Highly contagious virus that can cause clinical disease in bears, fox, coyotes, wolves, raccoons, skunk, mink and ferrets
- Makes intranuclear occluisons in hepatocytes & endothelial cells -> fatal hepatitis, hepatic necrosis and hemorrhagic disease
- Use canine adenovirus 2 to avoid “blue eye”
Identify the major source of parvovirus for susceptible animals and major ways to control transmission.
Transiently infected animals & environment (survives well outside of host)
2 clinical outcomes of alpha herpesvirus & transmission
Clinical outcomes
i. Active replication
ii. Latency/reactivation
Transmission
i. Close contact, Short-distance aerosol
ii. Between moist epithelial surfaces
iii. Closely confined populations
Explain the differences in pathogenesis and associated clinical signs between EHV-1 and EHV-4. Explain how EHV-1 can causes systemic disease, how neurologic disease can develop in EHV-1, and which cells are infected
EHV – 1
i. Starts in resp. epithelium -> infection of lymphocytes -> affects other organs systems thru infection of endothelium
EHV – 4
i. Localized upper respiratory infection
ii. Regional lymphadenopathy, nasal discharge, coughing
iii. Subclinical or mild to moderate,
iv. self-limiting = full recovery
v. low resp. infection rare
Explain how herpesviruses are maintained in the population.
a. Life-long infection (carriers)
b. Viral replication and shedding occurs w/ or w/out clinical Dz
Equine Herpes Virus Persistence
a. Both EHV-1 and 4 target neuronal cells in sensory ganglia innervating nasopharyngeal mucosa
b. EHV-1 is lymphotrophic (latency in T cells)
c. Reactivation with lytic infection occurs in adult horses with or without clinical signs
d. seen with “stress” – e.g. pregnancy, shipping, racing, training, etc.
EHV Systemic Dz
a. Spread outside of resp. associated w/ lymphocyte tropism
b. Virus accesses lymphocytes -> Replication in regional lymph nodes -> Cell-associated viremia -> Virus disseminates to endothelium in target tissues
-> causes abortion in uterus & neuro dz in CNS
Abortion due to EHV-1
a. Frequently occurs without respiratory or CNS disease
b. Uterine vasculitis necessary and sufficient for abortion
c. Fetus can be virus (-) but usually also crosses the placenta and infects the fetus, causing disseminated disease in the fetus
Equine Herpes Myeloencephalitis: clinical signs, key lesions, diagnosis
Clinical signs:
i. mild ataxia to paresis
ii. incoordination, gait abnormalities
iii. inability to rise from the sitting position
iv. may have paralysis and recumbency
Key lesions
i. vasculitis and ischemia
ii. neurons are not infected
Diagnosis
i. History and clinical signs very important!
ii. EHV-1 Serology (acute and convalescent)
iii. EHV-1 PCR
(Blood PBMCs or nasal swab)
Vaccine for Equine Herpes
i. Widely used
ii. EHV-1 and EHV-4 are cross-protective
iii. reduce severity of respiratory and abortive disease and/or prevent outbreaks of disease
iv. Frequent revaccination is needed
v. Maternal antibodies interfere with protection of young horses
vi. Vaccines not protective against neurologic disease
Bovine Alpha herpesvirus
Infectious Bovine Rhinotracheitis (IBR)
BHV-1
- major cause of resp dz and abortion
- does not infect endothelium
- abortion due to actual infection of the fetus in all cases
BHV-5
i. CNS disease affects brain, infects neurons
Feline alpha herpes virus 1; basics, how long is shedding, symptoms
o most important pathogen of upper respiratory disease in cats
o localized in upper respiratory tract
o Secondary bacterial infections
o Active shedding usually lags behind stressful event – can transmit virus for 3 weeks post event
o Viremia – very rare; occurs in hypothermic kittens
Symptoms
• conjunctivitis, ulcerative keratitis/dermatitis/ stomatitis, rhinitis, sometime abortion
Feline Calcivirus; basics, symptoms, hypervirulent strain
o Upper respiratory
o Small, non-enveloped, RNA virus
o Shed in ocular, nasal, oral secretions (think Calici if oral issues)
o Common persistent infections
o Virus persists in tonsils and other oropharyngeal tissues
Symptoms
• fever, sneezing, coughing, nasal and ocular discharge
• may have disease in lungs or joints
Hypervirulent strain
• infects endothelial cells = hemorrhagic disease
Canine Alphaherpesvirus
o In utero infection = abortion/fetal loss
o Neonatal infection = fatal multisystemic hemorrhage and necrosis
o Adult infection = typically not pathogenic but can cause mild respiratory disease (rhinotracheitis)
Macacine Herpesvirus
o Macaques
o Oral and gingival ulcers
o High seroprevalence in captive and wild cohorts
Fatal cross-species transmission
• humans can get fatal encephalitis
Betaherpes virus Family Basics
o Slow replication and “cytomegaly”
o Latency - established primarily in secretory epithelium
o Ubiquitous - frequently encountered when searching for causative agents
o generally NOT true cause of disease
o Disease, if any, is generally limited to immunocompromised hosts
o Example of disease causing: Elephantid herpesvirus 1
Elephantid herpesvirus 1
- Betaherpes virus
- Targets endothelial cells -> lethal hemorrhagic disease
- Seen in young Asian elephants
- Responds to antiviral therapy if administered rapidly
Gammaherpes virus Family basics
o Lymphotropic herpesviruses
o Often non-productive, non-lytic infections
o express various viral genes that activate cells, interfere with cell cycle, modulate the host immune response
o most are non-pathogenic in immunocompetent natural hosts
o if disease = lymphoid neoplasia and/or lymphoproliferative disease
o Example of disease caused: Malignant Catarrhal fever
Malignant Catarrhal fever: basics, clinical signs
- Gammaherpesvirus
- Infection of non-adapted host
- Caused in cows by Ovine Herpesvirus 2
- Fatal systemic dz
- Cannot pass from cow to cow (dead end hosts)
Clinical signs
• Epithelial erosion of upper respiratory and intestinal tracts,
eyes, lymph nodes
Malignant Catarrhal fever: pathogenesis
Pathogenesis
• OHV-2 infects sheep respiratory tract ->
• viremia ->
• infection of lymphocytes ->
• difficult to detect virus replication ->
• no clinical disease ->
• passed to cattle thru nasal secretions ->
• Proliferation of perivascular lymphocytes ->
• Necrotizing vasculitis systemically ->
• Ischemic necrosis
• Mucosal erosion & ulceration
Malignant Catarrhal fever: Diagnosis, Transmission, & Control
Diagnosis
• Clinical signs, exposure to carriers, vasculitis on histopathology, PCR detection of virus (lymphoid tissues)
• Serology - limited value since some animals may be subclinically infected
• Important differentials includes exotic diseases
Transmission
• Close Distance
• Cool moist environment
• Sheep shed OVH-2 most intensely at 6-8 months old
Control
• There is no vaccine available
• Management practices - separate sheep from cattle, bison, deer
Orthomyxoviridae
o Influenza
o Localized respiratory tract infections (except birds)
o Enveloped virus
o Single stranded (-) RNA genome
o Segmented genome
o 3 main types: A, B, and C (mainly influenza A)
Influenza A: key envelope proteins, host range, reservoir
Key envelope proteins:
• Hemagglutin or HA: critical for viral entry
• Neuraminidase NA: critical for viral exit
• divided into subtypes based on antigens present on HA & NA
Host range
• Dictated by presence of sialic acid which is carb receptor
Resevoir • Waterfowl • Harbor all H & N types • Subclinical persistent infections • Ag shift from bird to human occurs in pigs
Hemagglutin (HA) Vs Neuraminidase (NA)
Hemagglutin (HA)
• primary binding to sialic acid – dictates host susceptibility
• must be cleaved by extracellular host proteases for fusion protein to be exposed
• Presence of host proteases partially defines tissue tropism
• 3 HA monomers = trimer = viral ligand
• homotrimer binds sialic acid on target cells -> Endocytosis -> Drop in pH w/in vesicle -> HA conformational change -> Fusion & RNA release
Neuraminidase (NA)
• Cleaves scialic acid for release
How does antigenic variation occur in flu
- HA & NA carry neutralizing Ag
- Changes to Ag allow evasion of immune
Ag drift
o Minor change
o Point mutations
o Most common
Ag shift
o Major changes
o Re-assortment
o Appears suddenly
Equine Influenza: basics & clinical signs
- Most common viral resp of horses
- Relatively stable w/ some drift
- REPORTABLE
- Localized infections (upper & lower)
- any age but most common in young horses that are co-mingled
Clinical signs • High fever • Depression, anorexia • Nasal discharge • Cough - dry, harsh, non-productive • resolve in 2-3 weeks
Equine Influenza: pathogenesis, transmission, diagnosis, prevention
Pathogenesis
• Replication in U & L resp tract
• Replication = cell death, mucosal damage, ulceration
• Inflammation due to IFN
• Damage to mucociliary = secondary bacterial pneumonia
• Rare systemic signs
Transmission
• highly contagious via aerosols
• Shedding prior to signs & additional 4-5 days
• poor ventilation, high humidity, crowding
Diagnosis
• Nasal swabs for culture PCR
• ELISA to detect viral antigen
• Serology
Prevention
• Isolation
• Vaccination: killed, modifies live, canarypox vectored
Avian Influenza Basics; LPAI Vs HPAI
- Infects wild birds & poultry species (most often subclinical)
- Replicates in/sheds from both respiratory and enteric tracts
- There is a systemic form of AIV infection (HPAI)
Agent
• Avian influenza virus type A
• Variety of H and N types seen
Low pathogenicity avian influenza (LPAI)
o strains most common in domestic birds (poultry)
Highly virulent (pathogenic) avian influenza (HPAI)
o uncommon
o very high morbidity and mortality rates
o systemic spread ONLY in birds due to change in fusion proteins
Pathogenesis & Symptoms of Low Pathogenicity Avian Influenza (LPAI)
Pathogenesis
• cell-to-cell spread, lytic infection of epithelial cells
• secondary bacterial infections
• can mutate & spread systemically
Symptoms
• Localized infection of respiratory and enteric tracts
• coughing, sneezing, rales, lacrimation, sinusitis
• diarrhea can occur w/o respiratory signs
• Drop in egg/meat production
Emergence of High Pathogenicity Avian Influenza (HPAI)
- LPAI infects chickens
- Mutates in chicken
- Potential for severe zoonotic disease in humans, but NOT systemic disease
High Pathogenicity Avian Influenza (HPAI): symptoms & character
Symptoms o Vasculitis & lymphoid necrosis o Depression, lethargy, huddling o Cyanosis of comb & waddle or infarction o Edema of face o Hemorrhage of brain & mucosal surfaces
Character of HPAI
o Seen only with H5 and H7 subtypes
o Causes severe systemic infections
o short disease course = high mortality
High Pathogenicity Avian Influenza (HPAI): Diagnosis & Control
Diagnosis
o History of rapidly spreading respiratory disease
o PCR viral RNA
(choanal or cloacal swab)
o ELISA for viral antigen
(choanal or cloacal swab)
o Serology
Control o Biosecurity o Surveillance o Depopulation o Disinfection o No vaccines & no antivirals!
Canine Influenza: two HN combos, mild form vs severe
H3N8
• Described in 2004 in greyhounds
• Mutation from equine
H3N2
• Described in 2008 from dogs in Asia
• Avian origin
• Able to affect cats but may be mild
Mild Form
• Cough (dry, non-productive)
• 10-21days
• Nasal discharge, Fever, lethargy, anorexia
Severe Form (uncommon) • High fever, pneumonia, increased resp, consolidation of lung lobes
Canine Influenza: Transmission, diagnosis, treatment, prevention
Transmission
• Highly contagious
• Aerosols, respiratory secretions, Fomites
• Incubation usually 2-5 days
• Peak virus shedding 3-4 dpi but can shed virus for 7-10
Diagnosis • Nasal or pharyngeal swab • RT-PCR to detect viral RNA • Virus isolation • Immunoassays to detect virus antigen • Serology (later stage of illness)
Treatment
• Supportive
• Self-limiting, recovery in 2-3 weeks
Prevention
• Isolation
• Disinfection
Vx
• 2 doses, 2-3 weeks apart; then annual dose
Paramyxoviruses
o Enveloped, (-) RNA (non-segmented) genomes
o Many can induce syncytia
o Cytoplasmic & nuclear inclusions
Morbillivirus
- Classic systemic infections, multi-organ disease
- Major target organs include respiratory, enteric, CNS “pneumo-encephalitis”
- Canine distemper
- Newcastle Disease
Canine Distemper Viral Ligand & Receptor
• Several co-circulating CDV genotypes: differ in virulence
Viral Ligand:
o H (hemagglutinin) protein
o immunosuppression and reduced Ag presentation
Receptor:
o CD150
o Expressed on lymphocytes, macrophages and dendritic cells
Canine Distemper: Acute & Chronic Clinical signs & transmission (viral shedding).
Clinical Presentation
o Systemic infection- respiratory, GI, CNS
o ~ 50% of cases subclinical to mild
o Acute
• Resp & GI signs
• Neuro disease
o Chronic
• Later onset neuro signs
• Epithelial tissue may be affected
Transmission
o Direct contact, droplet, aerosol
o Virus is shed: in oro-nasal discharge
o Viral shedding: 7 days prior to clinical signs but Does NOT occur with chronic CNS disease
o Contact w/ recently infected (subclinical or diseased) animals maintains virus in population
Canine Distemper Pathogenesis
o Entry via aerosols into upper respiratory tract ->
o Replication in phagocytic cells of tonsils and trachea ->
o Replication in dendritic cells, monocytes, lymphocytes of regional lymph nodes ->
o Primary viremia = 1st fever, may be missed clinically ->
o Replication/amplification
in central lymphoid tissues ->
o Secondary viremia = 2nd fever, clinically significant and often this one is noticed ->
o Recovery if vaccinated
o If not vaccinated
o Seeding of epithelium of gut, skin, lung ->
o recovery & potential old dog encephalitis OR
o acute encephalitis OR
o severe catarrhal distemper
Canine Distemper: Diagnosis & Control
Diagnosis
o clinical signs, history
o Inclusions in blood cells during viremia
o culture IFA & RT-PCR (nasal & oropharyngeal swabs or epithelial samples)
o Rapid Ag tests
o Serology for Ab
Control
o vx
o occurs in unvaccinated animals & often coincides with loss of maternal Ab (~3-4 months of age)
o MLV should not be used for non-canid species
o Killed vaccines – only in dogs
o Canarypox-vectored H and F proteins are effective and safe
for other animals
Symptoms of Acute Distemper to
Chronic; lesions associated w/ chronic
Acute o Fever - biphasic o Rhinitis/nasal discharge o Conjunctivitis o Bronchitis, catarrhal pneumonia, secondary infections o Gastroenteritis with vomiting and diarrhea o Anorexia, depression o May cause Infection of brain
Chronic
o CNS disease usually follows acute signs by 1-3 weeks
o overwhelming infections and/or inadequate immune responses
Presentation of lesions due to epithelial cell infection:
o Hyperkeratosis of foot pads
o Hypoplasia of pre-eruption tooth enamal
Pathogenesis of Distemper CNS Disease
Sub-acute to Chronic encephalitis
• Reduced expression of CDV antigen in CNS
• autoimmune -> Immune-mediated demyelination
• Permanent CNS impairment
Old dog encephalitis - seen years later
• Rare, chronic slow progressive
Newcastle Disease
- distemper in birds
- Avian paramyxovirus serotype 1
- Has virulent and low virulent form
Clinical signs
o apathy, depression, lack of movement and appetite, reduced egg production, green or watery stool, respiratory difficulty, and conjunctivitis
o Viscerotropic: internal and external hemorrhages and swelling of the head and neck
o Neurotropic: partial wing paralysis, involuntary muscle tremors, and stiff or twisted head or neck
Basics & Lifecycle of Retroviruses
- Enveloped
- Diploid (+) RNA genome
- Not all are oncogenic but all have potential to be
Life cycle
o Attaches to receptor or hematopoietic cell ->
o Reverse transcription of RNA -> DNA
o DNA integrated into host DNA by integrase = provirus
o Cellular polymerase makes more RNA ->
o Viral proteins produced
Transformation by retroviruses relies on…
o Error prone Reverse transcription of (+) ssRNA into dsDNA
o Integration of dsDNA into host cell chromosome
o Transcriptional regulatory sequences such as the promoter in the viral LTR
Feline Immunodeficiency Virus (FIV); what cells does it affect, mode of proliferation
- non-oncogenic lentivirus
- infects lymphocytes
- higher incidence of lymphoma in infected cats
- Cis-insertional = uncontrolled cellular proliferation
Avian Leukosis/sarcoma virus: endogenous V exogenous & Transmission
• Alpharetrovirus
Endongenous
• Present in genoma of all chickens
• Rarely pathogenic
Exogenous • Transmitted between naïve birds • Causes disease when associated w/ tumor development • Transmission • Horizontal or vertical
Clinical Syndrome of replication competent Avian Leukosis/sarcoma virus; adult vs congenital
Adult or young birds (horizontal)
o Transient viremia, neutralizing ab
o Leukemia rare
Congenitally infected or infected during first few days
o Persistent infection due to immune tolerance
o Large amount of infectious virus shed in saliva and feces
o Tumor development: Usually lymphoid leukosis
o Most common form seen in chickens ~14-30 wks of age
Tumor development in Avian Leukosis/sarcoma virus
Lymphoid tumors
o most common
o Cis-insertional activation adjacent to cellular proto-oncogene i
o replication-competent virus
Mesenchymal tumors
o acquired proto-oncogene & transduction
o replication defective or competent virus
Myeloid/Erythroid tumors
o acquired proto-oncogene and transduction
o replication defective virus
Basics of replication defective Avian Leukosis/sarcoma virus
• Rapidly transforming & rarely transmitted from bird to bird
o Arise in an individual bird
o Lack full viral genes for replication
o MAY have acquired a cellular proto-oncogene (v-onc)
o Replication requires helper virus
Diagnosis of Avian Leukosis/sarcoma virus
- Necropsy lesions usually adequate
- Distinguished from Marek’s which has T-lymphocytes
- Histopathology - homogeneous population of B-lymphocytes
Incidence of Avian Leukosis/sarcoma virus
- Varies dramatically by country
- rare in commercial poultry
- common in Backyard flocks
Control of Avian Leukosis/sarcoma virus
Eradication:
o Most important in primary breeding flocks and egg-laying flocks for
vaccine production
o Expensive
Genetic resistance:
o Breed chickens which resist infection (very common)
o genetically resistant by changing confirmation of receptors
Management:
o “All-in-all-out” is standard practice
o Hygiene!!
Vaccines:
o Inactivated/attenuated
o limited success
Transducing Retroviruses
Acquisition & transduction of cellular genes
- During replication, cellular gene is inserted into the retrovirus genome ->
- genes no longer under the control of cell ->
- now under control of virus promoter transcription ->
- now a viral oncogene (v-onc) ->
- v-onc can be transferred from one cell to another by the virus = transduction
Avian Leukosis/Sarcoma Virus Replication Competent V defective: able to produce virons? mechanism of transformation? ocogene? tumor type? transmissbale btwn birds?
Able to produce infectious virions
• Competent – yes
• Defective – no
Mechanism of transformation
• Competent - Cis-insertional activation
• Defective - help from competent thru acquisition of cellular oncogene & transduction
Possesses oncogene
• Competent - no
• Defective - Yes (sarcoma)
Tumor type
• Competent -lymphoma
• Defective - sarcoma
Transmissible btwn birds
• Competent - yes
• Defective - no
JSRV & ENTV Basics
- betaretroviruses
- JSRV - sheep
- ENTV- 1 affects sheep, 2 affects goats
- exogenous & endogenous types
- Respiratory – progressive dyspnea, coughing, anorexia, nasal discharge
- JSRV -> pulmonary epithelial cell tumor (adenocarcinoma)
- ENTV -> nasal epithelial cell tumor (adenocarcinoma)
- Exogenous, oncogenic retroviruses
- have envelope protein that acts as oncoprotein = activation of signal transduction
JSRV & ENTV Transmission & Time to Dz
Transmission:
o Horizontal, close contact, aerosolized respiratory fluid
Time to disease
o prolonged incubation period = 1-3 years (affected animals usually >2 years old)
• Not all infected animals develop tumors (~30%)
JSRV & ENTV Diagnosis & Prevention/Control
Diagnosis
• Clinical signs + pathology (adenocarcinoma)
• PCR - peripheral blood leukocytes, lymph node, tumor
• serology of no help
Prevention/Control
• no vaccines
• Removal of infected animals from herd
Bovine Leukemia Virus (BLV) Basics & Character
- deltaretrovirus
- Exogenous
- Uses trans-cellular activation
- chronic disease evolving over 1-8 yrs
- Most infected animals = seropositive but no clinical signs
- Persistent lymphocytosis in ~30% (no clinical disease)
- 1 - 5% of cattle develop tumors (B cell lymphoma)
Bovine Leukemia Virus (BLV) Transmission
Horizontal
o Transfer of blood/infected lymphocytes
o Ex: Rectal palpation, Dehorning, Mechanical vector
Vertical & congenital transmission
o <10% calves virus positive at birth
o Infected milk/colostrum to calves (congenital)
Bovine Leukemia Virus (BLV) Diagnosis & Control
Diagnosis
• High incidence (1-5%) of multicentric B-lymphoma
• Serology tests or milk ELISA
• Agar gel immunodiffusion (AGID)
Control
• Periodic testing and elimination of positives
• VX not used for control
Feline Leukemia Virus Basics
- important causes of morbidity/mortality in cats
- Cause a wide spectrum of clinical manifestations - Malignancies, immunosuppression, anemia
- Predominantly domestic cats, but also non-domesticated big wild cats
- Endogenous (enFeLV) or Exogenous
Exogenous Feline Leukemia Virus; replication competent or defective, how to test, subtypes
FeSV
o Replication defective
FeLV
o Replication competent
o SNAP test detects core capsid protein which is in ALL subtypes
o Subtypes A, B, C, T based on genetic & Ag differences in the SU surface envelope protein
o FeLV-A is contagious and horizontally transmitted
Subgroups of FeLV
- Virulence of B and C higher than A
- B mainly associated with neoplasia
- C is rare = non-regenerative anemia
- T associated w/ immune deficiency (T lymph)
Transmission of FeLV
- via saliva
- Virus attaches to receptors on tonsillar monocytes, macrophages, lymphocytes -> systemic spread
- Also transmitted in milk, or in utero
- Kittens (<16 weeks of age) are more susceptible than adults to developing progressive infections
3 Pathogenesis of FeLV
Transient viremia
• replication in thymus, lymph nodes, salivary glands
Persistent viremia (progessor)
• Colonization of bone marrow ->
• Spread to epithelial cells of salivary glands, respiratory and intestinal tracts, pancreas ->
• FeLV-related disease results from cytopathic or transformative effects of virus
Latent infection (regressor)
• Virus persists in lymph nodes and bone marrow
• Little to no viral gene expression
Diagnosis of FeLV
- Capsid Ag in blood detected by Ag ELISA (good for progressor & viremic cats)
- Viral nucleic acid detection by PCR (good for latent infections)
- test w/ Ag ELISA ->
- if (-) test w/ PCR ->
- if (-) = true (-)
- if (+) = regressor
- test w/ Ag ELISA ->
- if (+) retest w/ ELISA ->
- if (-) = regressor (test w/ PCR)
- if (+) = progressor
2 Basic Outcomes of FeLV infection
• Determined by immune response, age, concurrent dz, dose of virus
Regressive infection • 70% of infected cats • Cats develop effective immune response and curtail virus replication • Transient viremia • Can be reactivated
Progressive infection • ~30% • Failure of immune response to contain virus • Persistent viremia • Develop fatal dz
FeLV Related Disorders
Immunosuppression (most common)
• Increased incidence of concurrent/opportunistic infections
Bone marrow suppression and disorders
• Usually nonregenerative and normochomic anemia
immune-mediated disease
• glomerulonephritis, polyarthritis, vasculitis
• Neurological disease
Neoplasia
• Lymphoma, lymphoid and myeloid leukemia
• Insertional activation near myc
FeLV Prognosis & Prevention
Prognosis
• Progressively infected cats have 50-80% decreased survival rate
• 2.4 year median survival time
Prevention
• Management
thru testing, good hygiene, single cat households
• Vaccination
Lentivirus Basics; 2 effects
o Genetically complex retroviruses
o Non-oncogenic
o High mutation rate (RT enzyme)
o Persistent, lifelong infections
o HIV-1 is a prototypical lentivirus
o if affects monocyte/macrophages & lymphocytes = immunsuppressive
o If it affects only monocyte/macrophages = chronic systemic inflammation
Pathogenesis of Lentiviruses; immunodeficiency subgroup Vs non-immunodefficiency
- Systemic infections involving immune cells
- All viruses initially replicate in monocyte-macrophage
Immunodeficiency disorder subgroup (FIV, SIV, HIV)
• Initial replication in mononuclear phagocyte system
• then becomes lymphotropic with destruction of CD4+ T lymphocytes
• Clinical dz from opportunistic infections and neoplasia
Non-immune deficiency/chronic inflammatory viruses (EIAV, OPPV, CAEV)
• clinical dz result of immune-mediated damage by Inflammation/cytokine or Virus-Ab complex
FIV Basics
- lentivirus
- Different subtypes based on env sequence
- Infects wild felids as well
- life-long infection
- can be subclinical
Transmission of FIV
Horizontal
o Mainly bite/fight wounds
o Social grooming not source of transmission
o Virus present in semen, transmission?
Vertical
o In utero – uncommon,
o Colostrum/milk
Phases of FIV
Acute phase
o 1-3months post infection
Chronic asymptomatic phase
o 3 mo - maybe forever
o progressive immune dysfunction
o no noticeable symptoms
Terminal / FAIDS
o clinical signs, Dz, death
Pathogenesis of FIV
- infection of monocytes/macrophages, lymphocytes- >
- Viremia ->
- Dissemination to CNS/lymphoid organs ->
- Progressive immune dysfunction
- Can also result in CNS dz
Clinical Dz associated w/ FIV
- Acute stage - lymphadenopathy, leukopenia, fever, depression, weight loss
- Neoplasia from immune suppression, or insertional activation
- Opportunistic infections
- Periodontal disease, gingivitis, stomatitis
- Chronic URT, GI, urinary tract infections/disease, CNS
- Weight loss
- Often no Dz!
Diagnosis / Prevention of FIV
- ELISA/SNAP, WB to detect Ab to FIV
- (+) test = infected, Vx (not used), false (+), maternal Abs
- Vx: not recommended
Equine Infectious Anemia Basics, 3 Versions
- lentivirus
- Reportable Dz
- Lifelong persistent infection
- Infects monocytes/macrophages -> inflammation
o Acute: High levels of virus replication, may result in death in 1-4 weeks post-infection
o Chronic: Recurrent cycles of fever, viremia, fever, thrombocytopenia, anemia, etc.
o Inapparent: Seropositive, no clinical signs
Equine Infectious Anemia Pathogenesis
- Infection of blood monocytes >
- monocytes disseminate to tissues throughout >
- differentiation to macrophages >
- activation of viral replication >
- pro-inflammatory cytokine production by macrophages >
- inflammation = clinical disease
Equine Infectious Anemia Clinical Signs & Evasion of Immunity
Undulating 1-2 week cycles
• fever, anemia, thrombocytopenia -> petechial, icterus
• Horse often develop ability to control cycles
Chronic
• Vasculitis, glomerulonephritis
• Death from anemia and wasting if cycling is frequent
Immune Evasion
• Ag variation of viral proteins - Env
• Periodic escape of virus from neutralizing Ab and CTL
• Escape mutants break through = continued cycling
Equine Infectious Anemia Transmission, Diagnosis, & Prevention
Transmission
• Biting flies transfer blood from one horse to another
Diagnosis / prevention
• Coggins test confirm with ELISA
• Immediate quarantine and testing of all animals within 200 yards
• Infected horses euthanized or quarantined and monitored for life
• Positive horses cannot cross state lines
• No vaccine
Coggins Test
- Test for equine infectious anemia
- Detects Ab against viral protein p26
- Required for transport across state lines
- infected animals may have false (-) result -> 3 wks-3mos to mount an Ab response
Small Ruminant Lentiviruses
- Caprine Arthritis Encephalitis Virus (CAEV) & Ovine Progressive Pneumonia Virus (OPPV)
- Persistent life-long infection
- Chronic inflammatory diseases w/ long incubation period
- affects Joints, Brain, Lungs
Pathogenesis of Small Ruminant Lentiviruses
- Transmitted thru colostrum/milk ->
- Infects monocytes/macrophages ->
- Inflammation in organs
Caprine Arthritis Encephalitis Virus (CAEV) Vs Ovine Progressive Pneumonia Virus (OPPV); diagnosis & prevention
CAEV
• Adults = arthritis in joints
• Kids – neuro dz = ascending paralysis (uncommon)
OPPV
• Lungs – progressive interstitial pneumonia (adults)
• Brain – hind leg weakness, paresis, etc (adults)
Diagnosis:
o serology ELISA for Ab
Prevention/Control
o Do not allow kids to drink milk
