Viral infections Flashcards
Feline herpes virus
What is swinepox?
caused by Suipoxvirus
- also caused by Vaccinia virus (that affects humans too)
lice and flies/mosquitos are vectors
causes erythematous macules
- progress through papular, vesicular, and pustular phases
- become umbilicated (“pox”)
What is porcine dermatitis and nephropathy syndrome?
caused by co‐infection with PRRSV and Anellovirus
get immune complexes, vasculitis, and systemic coagulopathy
- erythematous to reddish‐purple macules and papules –> plaques
- edema and proteinuria
What is foot-and-mouth disease?
caused by an Aphthovirus (an RNA virus)
primarily affects even-toed ungulates (not horses)
- humans are only very rarely affected (are by hand, foot, and mouth)
- can also affect hedgehogs and elephants
- pigs cannot serve as asymptomatic carriers (others can)
causes high fever for 2-6 days –> vesicles around mouth and hooves
- can lead to myocarditis and death
- can lead to abortion
- Morbidity varies from 50 to 100%
REPORTABLE! (foreign animal disease in US)
- severe implications for animal farming
- transmitted many way: contact, aerosol, fomites
- can be diagnosed via virus isolation or clotted blood
What is pseudocowpox?
caused by Parapoxvirus bovis‐2
most common infectious cause of teat lesions
- classical “ring” or “horseshoe” lesion
is zoonotic
What is the most common infectious cause of teat lesions in cows?
Parapoxvirus bovis‐2 (pseudocowpox)
What is bovine papular stomatitis?
caused by Parapoxvirus bovis‐1
- transmission is via skin abrasions
erythematous macules and papules
- may become papillomatous or become crusted
lesions are usually on muzzle, nostrils, and lips
- can be in mouth, on teats, etc
a chronic form in calves is proliferative and necrotic stomatitis
also associated with “rat-tail syndrome”
is zoonotic
What are the lesions in the cow most consistent with?
Parapoxvirus bovis‐2 (pseudocowpox)
What are the lesions in the cow most consistent with?
Parapoxvirus bovis‐1 (bovine papular stomatitis)
What does bovine herpesvirus‐2 tend to cause?
Herpes mammillitis
- occurs most commonly in lactating cattle
- sudden in onset, swollen, tender teats
- severity of lesions varies from dry erythematous skin to necrosis
- often painful
- decreased milk production and increased mastitis
- usually self-limiting
Pseudo-Lumpy Skin Disease
- looks like lumpy skin caused by Capripoxvirus
- mostly in southern Africa
What is malignant catarrhal fever?
Usually caused by ovine herpesvirus 2 (OvHV-2) outside of Africa
- exists as a ubiquitous subclinical infection in sheep
There are at least 10 viruses associated with it
- AIHV-1 is predominant in Africa from wildebeest
Affects many even-toed ungulates
Initial clinical signs include fever, nasal discharge, anorexia, depression
- photophobia, lacrimation, and conjunctivitis develop
- muzzle is crusted and burnt in appearance (may become necrotic)
- hard palate and tongue develop ulcers
- get erythematous‐to‐purplish macules that can ooze/crust
–>particularly common on perineum, udder and teats
- one report where cutaneous lesions were primary signs in cattle
- can develop GI and neurologic signs
REPORTABLE IN MANY STATES
What is bovine viral diarrhea?
Caused by Pestivirus
Have fever, diarrhea, nasal/ocular discharge, erosions/ulcers in oral cavity
- can develop erosions/ulcers elsewhere
Can have scales, crusts, hyperkeratosis, and alopecia
- esp occur on the neck, medial thighs, and perineum
In utero infections may cause generalized hypotrichosis
- spare the head, tail, and distal legs
Which viral infection in cattle can cause generalized hypotrichosis that spares the head, legs, and tail when contracted in utero?
Pestivirus (bovine viral diarrhea)
What does bovine herpesvirus‐1 tend to cause?
Infectious bovine rhinotracheitis
- respiratory form = fever, dyspnea, crusting of muzzle (“red nose”)
- genital form = pustules, necrotic white plaques on genitalia
In ruminants and swine, what is vesicular stomatitis clinically indistinguishable from?
foot-and-mouth disease
swine vesicular disease
vesicular exanthema of swine
In a multispecies farm setting, what can be used to differentiate vesicular stomatitis from foot-and-mouth disease?
If horses are affected
(but don’t, report both)
What do Orthopoxviruses cause?
cowpox
feline cowpox
vaccinia (buffalopox virus, rabbitpox virus, horsepox)
- not common anymore since smallpox immunization ceased
camelpox
mousepox
monkeypox
What are the member of the Poxviridae family?
Orthopoxvirus
Capripoxvirus
Suipoxvirus
Parapoxvirus
Molluscipoxvirus
Avipoxvirus
Leporpoxvirus
What do Capripoxviruses cause?
sheeppox
goatpox
bovine lumpy skin disease
What do Suipoxviruses cause?
swinepox
What do Parapoxviruseses cause?
pseudocowpox (-bovis 2)
bovine papular stomatitis (-bovis 1)
contagious viral pustular dermatitis (orf)
Parapox virus of red deer
What do Molluscipoxviruses cause?
molluscum contagiosum
What do Avipoxviruses cause?
Fowlpox
Pigeonpox
conjunctivitis or darkened areas of skin in Lovebirds
What do Leporipoxviruses cause?
Myxoma virus
Rabbit fibroma virus (Shope fibroma virus)
What type of viruses are Poxviridae?
enveloped DNA viruses
- envelope makes them resistant in the environment
share group-specific nucleoprotein antigens
many different ones including in reptiles
How are Poxviridae infections typically acquired?
entry through cutaneous or respiratory routes –>
gain access to the systemic circulation via the lymphatic system –>
- sometimes replication are cutaneous site can lead to entry into blood
become viremic –>
back to skin or target organs to cause disease
Where in the cell do poxviruses replicate?
cytoplasm of cells (despite being a DNA virus)
have replication “factories” that are independent of the host nucleus
What kind of inclusion bodies do poxviruses make?
more prominent eosinophilic inclusions are called Type A
- (3-7 mm in diameter)
- Borrel/Bollinger bodies
also have basophilic staining Type B cytoplasmic inclusion bodies
How do poxviruses induce cutaneous lesions?
degenerative changes in epithelium –> vesicular lesions
ischemia secondary to vascular damage
proliferative lesions via epithelial hyperplasia
What are the typical “pock/pox” lesion?
beginning as erythematous macules –>
become papular and then vesicular (sometimes nonexistent) –>
evolve into umbilicated lesions with a crust
- depressed center, erythematous border
- ulcerate more in cats
lesions often scar
What are the histopathologic findings associated with poxviruses?
cell swelling/ballooning degeneration
- esp of the stratum spinosum
Epithelia hyperplasia/acantholysis
- result in intraepidermal microvesicles
Necrosis, ulcers, crusts
Intracytoplasmic inclusions bodies
- typically find the eosinophilic Type A inclusion bodies
- may increase in size and density higher up in skin
Neutrophilic pustules
What is feline cowpox?
most commonly due to Orthopoxviruses
UK / Europe / very rare in North America
Reservoir hosts: voles, wood mice, ground squirrels, and gerbils
- occur when cats are wounded hunting rodents
Cause ulcers, plaques on head, neck or forelegs
- particularly ulcerative poxvirus
- can affect inside of mouth
Poxvirus
What is molluscum contagiosum?
caused by a molluscipox virus
worldwide in distribution
transmission occurs by intimate skin-to-skin contact and by fomites
- common in human children
immunoincompetent individuals more likely to be severely affected
- can affect immunocompetent animals too
horse and human ones are either the same or very similar
- horses may get it from humans
horses tend to have hundreds of lesions
- especially on the chest, shoulders, neck, and limbs
- 1- to 8-mm diameter papules that can be tufted
- usually become alopecic and covered with a powdery crust/scale
- may develop a small horn or turn into cauliflowerlike nodules/plaques
All lesions may not spontaneously regress
molluscum contagiosum (molluscipox virus)
What is lumpy skin disease in cattle?
caused by a Capripoxvirus
- similar disease can occur after vaccination with sheeppox
transmission occurs via insect vectors
- esp Stomoxys calcitrans
fever, anorexia, ocular/nasal discharge, hypersalivation, lymphadenopathy
Firm papules and nodules
- usually head, neck, legs, perineum, teats, udder, scrotum, and tail
can get leg edema –> areas of necrosis
IS REPORTABLE
What is contagious viral pustular dermatitis (“contagious ecthyma,” “orf”)?
caused by Parapoxvirus ovis
primarily seen in 3‐ to 6‐month‐old kid goats
- also affects sheep and camelids
tends to be seasonal (most common in kidding season)
papules –> vesicles –> pustules –> umbilicated, crusted
lesions become large and papillomatous
- esp if infected granulomatous tissue under crusts
Lesions are often painful
lips, muzzle, nostrils, eyelids, and pinnae most commonly affected (can affect inside of mouth)
- Oral lesions = red-gray-yellow papules & plaques surrounded by hyperemia
occasionally systemically ill
morbidity in kids can be 100%, mortality 1-20%
is zoonotic!
- 1/3 of humans get fever, lymphadenopathy, and erythema multiforme
Which breed of goat is more likely to have contagious viral pustular dermatitis (“contagious ecthyma,” “orf”)?
Boer and Boer cross goats
severe, generalized persistent dz with arthritis, pneumonia, & thymic involution
What is goatpox?
due to Capripoxvirus infections
- sometimes used to refer to impetigo in goats
Some strains cause disease only in goats, some in goats and sheep
Most often mild disease in the US
- disease is more severe in young animals
typically seen on lips, udder, and teats, and occasionally the perineum and medial thighs
doesn’t seem to be zoonotic
What is sheeppox?
due to Capripoxvirus infections
- sometimes used to refer to impetigo in goats
Some strains cause disease only in goats, some in goats and sheep
Sheep may be more affected than goats (young>adult)
- can have pyrexia, depression, anorexia, rhinitis, etc
- can have respiratory distress and facial edema
- mastitis can occur when on teats
Can look like ulcerative dermatosis
What is rabbit fibroma virus (Shope fibroma virus)?
caused by a leporipoxvirus
closely related to myxoma virus
Discrete tumors occur on the legs or feet, on the muzzle, and around the eyes
- tumors are dermal and not attached to SC
Tumors will typically regress after a period of about 6 months
What is myxomatosis?
Caused by a Myxoma virus (Leporipoxvirus)
severe and often fatal disease
- fatality rates of 50–95% in European rabbits
- there is an endemic strain in CA with 100% fatality
transmitted primarily by insects (esp mosquitos)
classic nodular form
- nodules
- swelling and edema of the eyelids and genitals
- milky or purulent ocular discharge
- respiratory signs and bacterial pneumonia
- fever, lethargy, depression, and anorexia
peracute disease (highly virulent strain) = death in 10-12 days
Vaccines are available in some countries
What are Morbilliviruses?
a genus in Paramyxovirinae (includes parainfluenza)
includes canine distemper, measles, rinderpest
enveloped ssRNA virus
What is Rinderpest?
a Morbillivirus
rare, in Africa and Asia
can cause erythema, papules, oozing, crusts, and alopecia over perineum, flanks, medial
thighs, neck, scrotum, udder, and teats
cattle, sheep, and goats are susceptible
What are the histopathologic findings associated with canine distemper virus?
Ortho and/or parakeratotic hyperkeratosis
Epidermal hyperplasia
keratinocyte hydropic degeneration
Syncytial cells ( fusions of multiple uninuclear cells)
Intranuclear and/or intracytoplasmic eosinophilic inclusions
- usually cytoplasmic, nuclear are rare
secondary pustular dermatitis (pyoderma) common
IHC is available
Canine distemper
What are the clinical signs of canine distemper in dogs?
respiratory, GI, neurologic, cutaneous
- initially replicates in lymph nodes
can develop widespread impetigo
with chronic disease can get “hard pad disease”
- pawpad>nasal>ventral abdomen hyperkeratosis
- cutaneous lesions not always noted concomitantly
can also have enamel hypoplasia, hypoplasia, “old dog encephalitis”, and thymic atrophy
What species are affected with canine distemper virus?
Dogs are considered reservoir host
Canidae (includes seals)
- in seals but they also have their own
Mustelidae (ferrets, skunks, otters, etc)
- ferrets are highly susceptible - mortality ~100%
- US has a canine distemper virus for ferrets
Procyonidae (racoons)
some Viveridae (palm civets)
some Ailuridae (red pandas)
some Ursidae (bears)
some Elephantidae (Asian elephants)
some primates (Japanese monkeys)
some large Felidae
What is phocine distemper virus?
A morbillivirus closely related to canine distemper virus seen in seals and sea otters
may not have respiratory disease
associated with cutaneous hyperkeratosis in the flippers and abdominal region of seals
What kind of inclusion body do morbilliviruses (ex. distemper) tend to have?
eosinophilic cytoplasmic (typical) OR nuclear
What kind of inclusion body do herpesviruses tend to have?
basophilic intranuclear
What kind of inclusion body do papillomaviruses tend to have?
basophilic intranuclear (dog and horse), cytoplasmic (cat)
What are the cutaneous lesions associated with FeLV?
Increased risk for many infectious disease
Increased risk of poor wound healing
Keratin mass on footpad; rarely nose and eyelid
Giant-cell dermatosis
- has syncytial-type cells in epidermis and ORS
- apoptotic keratinocytes surround them
Cutaneous lymphoma
What is the IHC when you are looking for FeLV in the skin?
gp70+ FeLV antigen
What are the cutaneous lesions associated with FIV?
Increased risk for many infectious disease
Increased risk for multiple MCTs
Papulocrusted dz with non-pruritic alopecia, scaling on head and limbs
- Histo: hydropic interface + occasional giant keratinocytes
What is FeSV (feline sarcoma virus)?
Variant of the FeLV virus that has incorporated proto-oncogenes
Cause of multicentric fibrosarcomas in young cats, liposarcomas in kittens
Possible relation to feline uveal melanomas
What is Herpesviridae?
Family of enveloped dsDNA viruses
three subfamilies:
- Alpha- (reproduce the fastest)
- Beta-
- Gamma-
include numerous viruses which can infect almost all animal
have an envelope, a nucleocapsid, DNA, tegument, and glycoprotein spikes
- spikes are named gB-M
icosahedral shape
What is the life cycle of herpes viruses?
viral particle contacts a cell with specific receptors –>
viral envelope glycoproteins bind to cell membrane receptors –>
virion is internalized and dismantled –>
viral DNA to migrate to the cell nucleus –>
all herpesviruses are nuclear-replicating –>
transcribe lytic viral genes and/or latency-associated transcript
- lytic viral genes are during symptomatic infections
- LAT is so that the virus can persist in the cell indefinitely
- long-term latency is symptom-free
What type of infectious organism are all viruses?
obligate intracellular
- so both virus and host have been subjected to selection and adaption
- viruses are selected for ability to evade the immune system
Which PRRs react to viruses?
viruses do not contain a lot of PAMPs
mostly recognize viral nucleic acids
- RIG-like receptors in cytosol for viral dsRNA –> trigger IFN-b
- TLR3 recognizes dsRNA viruses
- TLR7 and 8 recognize ssRNA viruses
- TLR9 recognizes CpG motifs in DNA
- NOD-like domains
- C-type lectins bind to viral glycoproteins –> block viral-cell interactions
Which cytokines are primarily produced in response to viral infections?
Interferons
Type I includes IFN-a and IFN-b
- IFN-a is produced by pDCs > lymphocytes and macrophages
- IFN-b can be produced by almost all viral-infected cells
Type II is IFN-y which is produced by antigen-stimulated Th1 cells
Type III are mostly local in GI, lungs, and BBB
When in the timeline of viral infections are type I interferons produced?
within a few hours
- produced when viral nucleic acids bind to TLR-7, TLR-9, and RIG-like
- via JAK/STAT pathways
high concentrations are achieved long before adaptive immunity develops
IFN-stimulated genes work through many pathways to have diverse effects on viruses including viral entry, replication, uncoating, protein assembly, or release as well as target affected cells. What are the 6 most important pathways?
1) The 2’5’ A pathway (degrades RNA)
2) The Mx GTPase pathway (blocks viral assembly)
3) The protein kinase R pathway (prevents translation)
4) The ISG15 pathway (destroys viral proteins)
5) The viperin pathway (blocks lipid rafts)
6) Tetherin (prevents viral release)
What is viral RNA interference?
an ancient innate antiviral pathway (including plants, inverts, and mammals)
viral dsDNA is broken up by an intracellular nuclease called DICER –>
become small interfering RNA –>
loaded into the RNA-induced silencing complex (RISC) –>
bind to viral RNA and destroys it
How does antibody-mediated adaptive immunity respond to viruses?
Virus proteins are antigenic and antibody responses target these
Can also produce antibodies against viral proteins on infected cells
- direct for these cells to be targets
- antibody-dependent cell-mediated cytotoxicity (ADCC)
IgG, IgM, and IgA are produced
- IgG is quantitively most
- IgM is qualitatively superior
How does cell-mediated adaptive immunity respond to viruses?
most important at controlling viral diseases
Viral antigens can be expressed on MHC I
- CD8+ T cells recognize this as foreign
Viruses can be sensitized by interferons
- IFN-y and TNF-a can allow CD8+ T cells to kill virus without killing cells
Some viral antigens can be superantigens and induce Th2 cells
IFN-y can activate macrophages against intra-mac viruses
What are some ways that viruses evade the immune system?
Negative cytokine regulation
- block IFN
Viral versions of cytokines, chemokines and receptors aka virokines
- equine herpes virus makes a receptor for eotaxin-1 (CCL11)
- pox and herpesviruses can make a version of IL-10
Some viruses hijack antibodies or complement to help enter cells
Interfere with antigen processing pathways (esp MCH I)
Evade NK cells (stress-related protein MIC-B)
Alter the B cell system
- antigenic variation
- viruses resistant to antibody neuralization
- lentiviral infections can infect faster than antibody production/binding
Alter the T cell system (retroviruses and distemper)
Go into latency
Act synergistically with some bacteria
Inhibit/delay apoptosis of their host cell
What are some potential problematic sequellae to immune responses to viruses?
Type I hypersensitivities due to production of IL-4 and IgE
Type II hypersensitivity if too much cellular destruction
- ex. distemper encephalitis
Type III usually associated with prolonged viremia
- glomerulonephritis in EIA, Aleutian mink disease, FeLV, etc
- generalized vasculitis in EIA, Aleutian mink disease, MCF, etc
- uveitis (“blue eye”) in dogs with adenovirus (usually resolves)
Virus where antibody presence increases susceptibility/severity
- antibody-dependent enhancement in FIV
What is Aleutian mink disease?
A parvovirus
in mink of Aleutian mink (gun-metal grey color)
these mink have Chediak-Higashi syndrome so predisposed
develop immune-complex-mediated lesions
immunosuppression prolongs survival
vaccination increases severity
How do you test for/detect viral infections?
PCR (viral DNA) or reverse transcriptase PCR (RNA viruses)
antigen/antiviral ELISA test typically used when bedside testing
lateral chromatography tests
hemagglutination inhibition
immunofluorescence
testing for antibodies to viruses
What types of herpes viruses are present in birds and reptiles?
alphaherpesviruses
- may the the earliest branch
What are the viruses of major important to veterinary dermatology within Alphaherpesvirinae?
Suid herpesvirus 1 (SuHV-1) - aka Aujeszky’s disease/pseudorabies
bovine herpesvirus type I (BHV-1) - rhinotracheitis
bovine herpesvirus type 2 (BHV-2) - mammillitis, pseudo-lumpy skin
Equine herpesvirus 3 (EHV-3) - equine coital exanthema
Feline herpes virus type 1 (FHV-1) - rhinotracheitis and herpes dermatitis
All herpes infections in reptiles and birds
*herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) in humans
What is feline herpes virus type 1?
An alphaherpesvirus
Causes feline rhinotracheitis
Causes URI symptoms, keratoconjunctivitis, rarely cutaneous/oral ulcers
Cause of herpesvirus ulcerative and necrotizing facial dermatitis
- ulcers are usually on face, distal limbs, trunk
- initial lesions near trigeminal nerve then spread due to grooming?
Latency in trigeminal ganglia (can activate with immunosuppression)
Maybe can cause exfoliative erythema multiforme
What is the histopathology finding associated with herpesvirus ulcerative and necrotizing facial dermatitis?
Ulcer + necrosis of epidermis and follicles
Crusts +/- vesicles
Eosinophilic infiltration (+/ flame figures), neuts can predominate
Eosinophilic/amphophilic intranuclear inclusions
- Marginated chromatin
- Not always seen
- Look at transition intact epithelia!
- +/- sebaceous glands
+/- Syncytial cells (multinucleated epithelia)
PCR, IHC may help diagnosis
Which a animal is particularly susceptible to feline herpesvirus-1 (FHV-1)?
Cheetahs (endemic in zoos)
Vaccination protocols are recommended
feline sarcoid
Biopsy from a cat.
Feline papilloma
Koilocytes
from a cat with BISC
BISC
Shope papilloma virus
Biopsy from a horse.
Papilloma
Biopsy from a nodular lesion on a horse.
Sarcoid
