Virology Flashcards
Poxvirus transmission
Resistant in environment (despite envelope)–>
Transmit via abraded skin, respiratory route (droplets), mechanical (fomites, insects, etc.)
Genus Capripoxvirus spp.
sheep pox
lumpy skin disease
goat pox
(all serologically identical)
Genus Caprivirus Epidemiology
endemic in SE Europe, Middle East, Africa, Asia
Generalized disease
Can spread between sheep/goats/cattle but often remain in respective host sp.
Mortality up to 50% in indigenous breeds, up to 100% in European breeds
Genus Caprivirus Pathogenesis and clinical signs
Infection by abrasion, aerosols, mechanical–> replicates locally in skin/lungs–> regional lymph nodes–> viremia–>shed from skin lesions and nasal/ocular discharge
Incubation ~ 1 week–> fever, edema of eyelids, conjunctivitis, nasal discharge, skin lesions, lung consolidation/hemorrhage
Genus Avipoxvirus spp., modes of transmission
Fowlpox virus, other avian poxviruses
Mechanical transmission by mosquitoes, aerosol transmission
Orf virus (scabby mouth, contagious ecthyma) Transmission, pathogenesis, maintenance in population
= contagious pustular dermatitis (worldwide)
Transmitted by direct/indirect contact (abrasions)- infectious in scab for months
Epitheliotropic- proliferates locally in epidermal keratinocytes–> wart-like lesions near lips, muzzle, feet, genitalia, teats
papules–>vesicles–>pustules–>scabs
Primarily in young sheep, maintained by chronic carriers
Myxoma virus epidemiology and pathogenesis
Myxomatosis = poxvirus disease of rabbits
Benign fibromas in American wild rabbits, severely degenerative in European species
Mechanical transmission by mosquitoes and fleas (not contagious)–>listless and febrile–> often death w/in 48 hours (survivors have sub-Q gelatinous swellings)
Mortality rate ~99% in wild rabbits w/ virulent strain
African swine fever (asfarviridae) epidemiology, pathogenesis
Infects Suidae and soft ticks
Persistent tick infection–> 1) sylvatic cycle- viremia in juvenile warthogs (little-no dz in African breeds)
–> 2) domestic cycle- up to 100% mortality due to diffuse hemorrhage from platelet damage and complement activation, fever (European breeds)
Persists in meat for months–>pigs can become infected from carcass of dead infected pigs
No neutralizing Ab made, no vaccine, risk of international spread in pig products
Herpesvirus epidemiology/pathogenesis
Labile (enveloped)–> spread by close or mucosal contact (e.g. droplets)
Lifelong latent infection in neural or lymphatic tissue with continuous or periodic shedding (reactivated in times of stress)
Copies DNA in infected neurons, no viral gene expression except latency associated transcripts (LATs- inhibit apoptosis)
Can be shed while sub-clinical or recrudescent (reemerging clinical signs)
Bovine Herpesvirus 1 (infectious bovine rhinotracheitis)
Pathogenesis, clinical signs
Respiratory infection by aerosol route--> viremia (dissemination)--> rhinotracheitis, vulvovaginitis, balanoposthitis (virus shed in semen), conjunctivitis, abortion, enteritis, nasal discharge, hyperemic nasal mucosa, dyspnea, coughing, focal areas of epithelial necrosis and inflammation Recovery 5-10 days Intensive environments (e.g. feedlots) morbidity ~100%
Bovine herpesvirus 2
Bovine mammillitis virus/ pseudo-lumpy skin disease virus
2 forms:
Mammillitis (localized lesions on teats)
Generalized nodules and necrosis
Bovine herpesvirus 5
Bovine encephalitis virus
direct neural spread via trigeminal nerve from nasopharynx–> fatal meningoencephalitis in calves
Equine herpesvirus 1
epidemiology, pathogenesis
Most important viral cause of horse abortion worldwide
Infection via respiratory tract–> respiratory and neural dz–> viremia and systemic infection–> endothelium of endometrial vasculature–> vasculitis–> infarction–> abortion
Aborting mare infectious for 1-2 days from reproductive tract, 2 weeks from respiratory tract
Minimize risk by keeping pregnant mares separate from other horses and in small groups by foaling date
Reduce latent infection risk by minimizing stress
Equine Herpesvirus 4
Equine rhinopneumonitis- similar to EHV1 but only acute respiratory dz
nasal discharge and lymphadenopathy in foals (esp. weanlings and yearlings)
Only ELISA can differentiate EHV1/EHV4
Equine Herpesvirus 3
Equine coital exanthema
Veneral alphavirus
Lifelong latently infected carriers
Spread by mucosal contact
Feline Herpesvirus 1
clinical signs and prevention
Feline rhinotracheitis
Acute respiratory dz (similar signs to calicivirus)- nasal/ocular discharge, sneezing, dyspnea, oral ulcers
Lifelong latent carriers
Inactivated and live attenuated vaccines available
Live vaccine can cross placenta in pregnant queens
Gallid Herpesvirus 1
Clinical signs
Infectious laryngotracheitis (young chickens) Acute respiratory dz- nasal/ocular discharge, sneezing, dyspnea, gasping/coughing Often hemorrhagic exudate w/ diphtheritic pseudo-membrane occluding trachea
Canine adenovirus 1 pathogenesis
Infectious canine hepatitis (4-9 day incubation)
Contaminated urine/feces–> nasopharynx/mouth/conjunctiva–> tonsil crypts/peyer’s patches–> viremia–> vascular endothelial cells–> hemorrhage/necrosis of major organs (esp. liver- inflamm., hepatocellular damage, failure)
–> 1) virus shed in urine/feces/saliva
–> 2) shock–> death
–> 3) Neutralizing Ab response–> recovery
Canine adenovirus 1
clinical presentations, diagnosis, prevention
3 syndromes:
1) peracute dz- 3-4 hours, found dead
2) acute dz- fever, vomiting, dysentery, collapse, petechial gums, icterus, may be fatal
3) mild or inapparent dz
Dx: Ag detection in urine (virus isolation, PCR)
- Ab detection- ELISA, HAI
Prevention: vaccine part of C3 protocol, CAdV2 vaccine cross-protective and safer than CAdV1 (no risk of corneal edema)
Canine adenovirus 2
Infectious canine tracheobronchitis
Localized respiratory dz (part of kennel cough complex)- bronchitis/bronchiolitis
Not systemic, doesn’t affect wildlife
Vaccine provides complete homologous protection against CAdV1
Equine adenovirus 1 & 2
EAdV1: found in young horses w/ or w/o respiratory dz
EAdV2: in lymph nodes and feces of foals w/ respiratory disease and diarrhea
Mostly asymptomatic or mild
Could be fatal for Arabian foals with SCID
Family Papillomaviridae pathogenesis
Infections through skin abrasions–>infection of basal cells in squamous epithelium–> clonal proliferation (delayed maturation)–> papilloma formation (finger-like projections)–>viral shedding
Often in young animals, usually regress after several weeks
Bovine papillomavirus
pathogenesis, neoplastic transformation, diagnosis
Transmission via fomites, sexual (venereal warts)–> squamous papilloma in mucocutaneous areas–> fibropapillomas (pedunculated) on udder, teats, head, neck, genitalia–> spontaneous regression after 1-6 months
Neoplastic transformation: BoPV + bracken fern poisoning (enzootic hematuria)–> neoplasia (BoPV2= bladder cancer, BoPV4= alimentary cancer)
- UV + BoPV–> ocular squamous cell carcinoma in lateral esclero-corneal limbus, nictitating membrane, or lower eyelid
Dx: direct observation, histopathology, PCR
Equine sarcoid
Presentations, behavior, treatment
Papillomavirus (BoPV implicated)- most common equid skin tumor
Head, limbs, ventral abdomen of 4+ y.o. horses esp. at site of previous scarring
Locally aggressive but does not metastasize
Transmitted by fomites, possibly flies
Possible presentations: occult, verrucose, nodular, fibroblastic, malevolent, +/- pedunculated
Treatment (excision) ineffective- recurrence common
Feline Panleukemia virus
epidemiology, pathogenesis, clinical signs, prevention
Highly contagious generalized systemic/enteric dz worldwide (1 serotype) Enters cats (often young as maternal Ab wanes) via oropharynx--> replicates in pharyngeal lymphoid tissue--> viremia--> mitotically active cells (intestinal crypt, bone marrow, fetal cerebellum/retina)--> incubation ~5 days--> bone marrow suppression, GIT signs, cerebellar hypoplasia (in fetus via transplacental transmission)--> shed in saliva, urine, vomit, feces (several weeks) Inactivated and live vaccines available
Canine parvovirus 2
Epidemiology and prevention
High morbidity and mortality in all Canidae 3 variants (2a, 2b, 2c) Vaccine protects against all variants but not 100% immunity- part of C3 given @ 6-8 weeks, 14-16 weeks, 1 year, every 3 years
Canine parvovirus 2 pathogenesis
Feco-oral transmission–> pharyngeal lymphoid tissue–> viremia–> replicates in intestinal crypt cells–> hemorrhagic gastroenteritis, vomiting–> virus shed in feces for 3-7 days after infection (persists in environment for months)
Mucosal collapse w/ contraction/fusion of SI villi–> malabsorption, hemorrhage–> dysentery w/ fetid smell (usually enough to make presumptive Dx)
Porcine parvovirus
epidemiology, pathogenesis, diagnosis, prevention
Worldwide reproductive failure, 1 serotype, stable in environment
Infection via oronasal route–> local replication in tonsillar lymphoid tissue–> viremia and transplacental transmission (takes ~15 days to reach fetus)
- <30 days gestation–> resorption
- 30-70 days gest.–> stillbirth & mummification
- >70 days–> stillborn, abnormal, or normal fetus
Dx: infected feti have high virus titer (PCR, HAI)
Prevention: exposing guilt or vaccinating before pregnancy induces immunity
Psittacine beak and feather disease
pathogenesis and clinical signs
Cockatoos, parrots, budgerigars
Replicates in basal epithelial layer–> basophilic intracytoplasmic inclusions, lymphoid depletion–> difficulty feeding and death
Feather changes: stunted pin feathers, bloody/sheathed/fractured adult feathers
Beak/claw deformities: broken, overgrown and shiny, delaminations, palatine necrosis
Porcine circovirus 2
Post-weaning multi systemic wasting syndrome
Progressive dz in 6-week old piglets- weight loss, enlarged lymph nodes, dyspnea
Chicken anemia virus
Shed in feces & feather dander–> transmitted by direct contact or fomites–> aplastic anemia, generalized lymphoid atrophy in 2-3 week old birds
Bluetongue epidemiology
Family Reoviridae, Genus Orbivirus
Non-enveloped RNA virus with >25 serotypes of varying virulence
Infects she, cattle, and goats in tropics/sub-tropics
Arbovirus- replicates in arthropod (Culicoides spp.) salivary glands & has extrinsic (in arthropod) and intrinsic (in mammalian host) incubation periods
Bluetongue pathogenesis
Infection from arthropod–> incubation ~1 week–> replicates in lymphoid tissue and endothelial cells–> viremia for 14-28 days–> spread when bitten by Culicoides spp.
Bluetongue clinical signs
Various vascular lesions: hyperemia of oral cavity (frothy/salivation), nasal discharge (variable consistency), cyanosis of tongue, hyperemia of coronary bands, edema of head/neck
Vary from sub-clinical to fatal (~2-8 up to 30% mortality), more severe in sheep than in goats
Pregnant ewes may abort or have lambs with abnormalities (hydranencephaly)
Bluetongue diagnosis and control
Dx: presumptive based on clinical signs or post-moltem findings, isolation, PCR, serology (ELISA), neutralization assay
Control: live attenuated vaccinations available (must know local prevalent serotypes), sentinel cattle herds
African Horse Sickness epidemiology
Same as Bluetongue but host species = horse
9 serotypes
African Horse Sickness
clinical signs
3 forms of febrile dz:
- Peracute pulmonary form (near 100% mortality): nasal discharge–> respiratory distress (pulmonary edema, pleural effusion)
- Subacute cardiac form: conjunctivitis, abdominal pain & progressive dyspnea, sub-Q edema (infraorbital fossa, palpebral conjunctiva, intramandibular, hydropericardium)
- Mild/sub-clinical dz in African donkeys and zebra
African Horse Sickness pathogenesis
Infection from arthropod vector–>incubation ~4-9 days–> replicates in regional & other lymphoid tissue–> blood cell-associated viremia w/ onset of fever–> heart, brain, lungs, endothelial cells
African Horse Sickness
diagnosis and control
Presumptive Dx based on clinical signs, rapid death, typical lesions (supraorbital edema, frothy nasal discharge, respiratory distress), seasonality
Virus isolation or RT-PCR from washed RBCs
Control: attenuated polyvalent vaccine available, predict outbreak through knowledge of vector life cycle
Genus Rotavirus pathogenesis
Feco-oral transmission (food, water, etc.) in 1-8 week old calves–> incubates ~12-24 hours–> capsid VP4 cleaved by chymotrypsin in epithelium of apical tips of SI villi–> severe enteritis, secretory diarrhea (“white scours”), inappetence, depression, dehydration (–> death)–> high titer shed in feces, persists for months, resistant to disinfection, small infective dose required
Rotavirus control
Improved hygiene
IgG in colostrum/ lactogenic immunity (vaccinate dam)
Prevent dehydration and electrolyte imbalance
Foot and Mouth Disease
epidemiology
Family Picornaviridae, Genus Aphthovirus
Highly contagious dz of cloven-hooved farm animals (NOT horses)
High morbidity, low mortality- huge production losses
Multiple host spp. and modes of transmission
7 serotypes (O, A, C, SAT1, SAT3, Asia1) with little cross-tolerance
Small infective dose, rapid replication
Pigs = amplifier host, sheep often inapparent/persistent carriers
FMD pathogenesis
Oral transmission by aerosols or fomites–> incubation period 2-8 (up to 14) days–> shedding up to 4 days before onset of clinical signs
FMD control:
vaccination (inactivated) vs. slaughter
Vaccinated animals can be carriers- serologically identical to diseased
FMD-free w/o vaccination = easier to trade than if vaccinated; serological test and slaughter (positive and in-contact animals)
Endemic FMD- eradication campaign w/ ring or blanket vaccination
FMD clinical signs and diagnosis
Fever, inappetence, depression, decreased production, excessive salivation
Vesicles on tongue and oral mucosa, interdigital region, coronary bands, teats, nasal mucosa/muzzle
Vesicles coalesce/rupture–> large ulcers
Myocarditis–> sudden death in calves and piglets
Dx: sample from epithelium with vesicles, Ag detection by ELISA, culture, PCR
Eastern & Western Equine Encephalitis
Family Togaviridae, Genus Alphavirus- enveloped RNA viruses
Maintained in mosquito-passerine bird cycles (neither show dz)
Dz outbreaks when sufficient vectors spill over to horses and humans (dead-end hosts)
Seasonal peak in late summer after heavy rainfall
Venezuelan Equine Encephalitis epidemiology
Outbreaks when vectors spill over to horses and humans
Viremia in infected horses = sufficient titer to be amplifying host for new vectors
Enzootic/endemic cycle: between small mammals and Culex spp.
Epizootic/epidemic cycle: virus mutates to enter cycle between mosquitoes and large mammals
Equine Encephlitidies pathogenesis
Mosquito bite–> replication in local cells–> regional lymph nodes–> primary viremia–> replicates in muscle, CT, endothelium–> secondary viremia–> CNS invasion–> neural necrosis, mononuclear infiltration, perivascular cuffing, interstitial edema (incubation up to 9 days)–> mild fever and depression to fatal encephalomyelitis with CNS signs (photophobia, head pressing, etc.)
Equine Encephalitidies diagnosis and control
Dx: viremia transient- difficult to isolate in blood
- serology (IgM ELISA), neutralization on paired sera
Control: vaccination available in endemic areas
- Live VEE, inactivated WEE & EEE
- Vector ctrl- insecticides, repellents, sentinel chickens
Japanese encephalitis epidemiology
Flavivirus endemic to SE Asia, India, China
reservoir = water birds
amplifying host = pigs (reproductive failure)
Spillover to horses and humans (dead-end hosts)–> severe fatal encephalitis (fever, lethargy, hyperexcitability, recovery or death)
Maintained in mosquito-pig life cycle
Post-mortem serology for Dx
West Nile Virus
epidemiology, dz processes, prevention
Mediterranean, Asia, Africa, US (warm/wet climates)
Urban bird-mosquito cycle
Bird = amplifier–> blood titer sufficient to be picked up by more vectors
Fatal encephalitis in horses, hemorrhagic fever in humans
Vaccine: killed virus in 2 doses w/ annual booster
- no IgM, high levels neutralizing Ab after 2nd dose
Murray Valley Encephalitis Virus epidemiology
Victoria and SA
Arbovirus (vectors = Culex annulirostris, C. australicus)
Maintained in herons, cormorants, darters
Often sub-clinical (1 in 800 severe dz)
Transient viremia- hard to detect (serological & virological)
Bovine viral diarrhea virus
different disease presentations (non-pregnant)
Acute- BVD
Chronic- persistent mucosal dz (profuse watery diarrhea, ulcers, fatal w/in weeks)
All ages susceptible
Fever, immunosuppression, leukopenia, diarrhea, naso-ocular discharge, ulcerative stomatitis, decreased milk production
BVDV
pathogenesis (pregnant)
Transplacental transmission
- <80 days: abort, resorb
- 80-125 days: cytopathic strain–> lesions/weakened or dead calves, non-cytopathic strain–> tolerance to virus
- > 125 days: active immune response, develop Ab and survive
BVDV diagnosis, prevention, control
Dx: difficult- PCR, isolate virus/detect Ag, immunofluorescence, serology
Killed and live vaccines available but not fully protective
Must remove persistently infected animals to eradicate
Classical swine fever
epidemiology, pathogenesis, clinical signs, prevention
Contagious, exotic dz
Virulent, moderate (chronic dz), and low virulence (decreased fertility) strains
Ingestion/inhalation due to direct contact–> replicates in tonsils–> lymph & endothelial cells–> hemorrhages, DIC, thrombosis (2-10 day incubation)–> fever, hyperemia, purpura, convulsions, posterior paresis, paralysis, tremors, death wi/in weeks
Effective live vaccine available
Influenza A pathogenesis
Aerosols (or feco-oral for birds)–> spread through respiratory tract in 1-3 days–> fever w/ necrosis of epithelial cells–> secondary bacterial infections may–> bronchopneumonia
Influenza A epidemiology
Orthomyxovirus- enveloped, RNA Subtypes: HA(16+) + NA(9) - external Ag^ do not cross-react - strains (usually geographical) w/in subtype may cross-react Seasonal Shed ~8-10 days (often sub-clinically) High morbidity, low mortality Common interspecies transmission (horse, human, bird, pigs)
Influenza A
common clinical signs
Cough, sneezing, nasal discharge, fever, loss of production (eg low virulence avian influenza)
Retrovirus
envelope & genome characteristics
Envelope has peplomers (glycoprotein spikes) (labile--> require close contact) Diploid RNA genome w/: - gag--> structural proteins - pol--> reverse transcriptase - env--> envelope protein
Rapid mutation of retroviruses
RT makes frequent errors–> inherent high rate of mutation
Concurrent infection w/ 2 retroviruses–> high rate of recombination btwn viruses (partially due to diploidy)–> different peplomers = ability to bind new cell types–> potential for jumping species
Exogenous vs. endogenous retroviruses
Exogenous = can create infectious virions and transmit horizontally Endogenous = genetic element (provirus) w/in host genome that can replicate and insert into distant part of genome
Neoplastic dz (alpharetrovirus) in poultry 3 strains
Replication competent virus–> lymphoid leukosis, osteopetrosis, renal tumors
Replication incompetent virus (carry onc gene)–> neoplasia of myeloid cells and sarcomas
Replication competent rapidly transforming virus (w/ onc)–> Rous sarcoma virus
Neoplastic dz in poultry
pathogenesis
- If infected <5 days old–> immunological tolerance–> lifelong infection–> leukemia and other dz (constantly shedding)
- If infected >5-6 days old–> transient viremia and neutralizing Ab production
- DNA provirus insertion into germline–> genetic transmission
- Horizontal transmission inefficient but facilitated by intensive conditions
Ovine pulmonary adenomatosis (Jaagsiekte- Betaretrovirus)
pathogenesis and control
Respiratory infection–> multiple small tumors (type II secretory epithelial cells) in lungs produce copious fluid w/ surfactant–> spasmodic coughing (no immune response)
Incubates 1-3 years
Transmission slow so removal of sick sheep/offspring is sufficient to control
Feline leukemia and sarcoma
dz processes
Gammaretrovirus
Multicentric/thymic lymphoma, alimentary & lymphosarcoma of eye/skin/CNS, myeloproliferative dz w/ anemia, immune complex dz & immunodeficiency
W/in 6 weeks will either:
1) persistent infection w/ viremia but no neutralizing Ab response
2) transient viremia w/ neutralizing (or anti-FOCMA) Ab response–> no dz signs (still contagious)
Dx: clinical signs, post-mortem, test blood for Ag
Bovine Leukemia (BLV) presentation, diagnosis, control
Deltaretrovirus
Mostly subclinical +/- leukocytosis, few develop lymphoid tumors
Decreased productive life and condemned carcass
Likely relies on proviral oncogenes targeting B cells
Can detect Ab in serum or milk
Natural transmission is slow- control by testing serum every 3 months and removing if Ab+
Lentivirus behavior
slowly progressive acquired immunodeficiency
mutations in env gene–> Ag variation
Maedi/Visna
dz processes
= Ovine progressive pneumonia
maedi = dyspnea- lung consolidation due to lymphocyte/macrophage infiltration
visna = wasting- demyelinating leukoencephalomyelitis
Maedi/Visna pathogenesis
Spread by respiratory droplets or milk–> 2 year incubation–> present in blood/semen/bronchial secretions/tears/saliva/milk–> slow progression–> eventually fatal
Detection by Ab in serum
Caprine arthritis (encephalomyelitis) dz processes, control, diagnosis
Progressive leukoencephalomyelitis (<4 m.o.) or arthritis (>1 y.o.)
Transcolostral transmission- control by preventing suckling and supplementing kids with pasteurized colostrum
Dx: history in flock, serum Ab
Equine infectious anemia
pathogenesis, clinical signs, diagnosis
Transmission by mechanical vectors (stable flies, tabanids, mosquitoes, etc) or iatrogenic
Incubates 7-21 days–> fever associated w/ macrophages and lymphocytes–> lifelong cell-associated viremia (sub-clinical or recurrent dz)
Fever, weakness, anemia, jaundice, thrombocytopenia, IgM/IgG deposition on RBCs/platelets/endothelium
Dx: serum Ab (Coggins test)
Feline immunodeficiency virus
epidemiology, pathogenesis, detection
Worldwide, many cat spp.
Shed in saliva–> transmission through bites–> lifelong infection
Early: fever & lymphadenopathy
Terminal (months-years later): weight loss, CNS signs, leukopenia, secondary infections
Detection by serum Ab, vaccine not widely used (only 2/5 serotypes)
Jembrana disease
pathogenesis, prognosis
Fatal dz in Balinese cattle (high morbidity and mortality)
5-12-day incubation–> hemorrhages & splenomegaly–> fever, lethargy, anorexia, swollen lymph nodes, panleukemia
Rapidly progressive, recovered animals clear the virus (unique for Lentivirus)
Oncogenic Retroviruses & major genes
FeLV, BLV, avian leukosis virus, porcine lymphosarcoma, murine leukemia, koala retrovirus
RNA genome:
gag = core nucleocapsid structural protein
pol = reverse transcriptase
env = envelope proteins
+/- v-onc = induce cancer
Replication incompetent exogenous retroviruses
gag_pol__v-onc
Require co-infection w/ other virus to induce cancer
Replication competent exogenous retroviruses (2 types)
- gag_pol_env
- insert provirus near c-onc or TSG to alter expression
- chance event–>longer incubation period - gag_pol_env_v-onc
- cancer after short incubation (short as 2 weeks)
- e.g. Rous sarcoma virus of chickens
Oncogenic Flaviviruses
Hepatitis C virus can–> late stage hepatocellular carcinoma (humans)
Oncogenic Poxvirus mechanism
Replicate entirely in cytoplasm (DNA genome)
Early viral protein homologous to epidermal growth factor–> cell proliferation–> local benign tumor-like lesions
Hepadnavirus oncogenesis
Associated w/ natural hepatic carcinomas
e.g. duck hepatitis B + mycotoxin ingestion–> malignancy
Marek’s dz oncogenesis
Herpesvirus in chickens w/ many v-onc genes
- meq- activates signal transduction pathways
- vTR- encodes subunit of telomerase to maintain telomere length
Coronavirus characteristics
Enveloped (labile but can survive in GIT)
RNA genome
Replicate in cytoplasm
Glycoprotein spike “crown” for attachment- determines tropism, antigenicity, target for neutralization ( S “spike” protein)
Coronavirus pathogenesis
Aerosol, feco-oral, or close contact transmission–> GIT and URT of birds and mammals
Clinical infections often in young animals as maternal Ab wanes
Can spread to LI (unlike rotaviruses, which also infect apical enterocytes)
Enteric dz: 20-100% morbidity, 1-2% mortality
Good at jumping species
Bovine Coronavirus
enteric infection
Calf diarrhea from <3 weeks-3 months old (maternal Ab)
Destroys mature absorptive enterocytes of SI and LI villi–> malabsorption–> water and electrolyte loss–> circulatory failure and death (calves) or intestinal hemorrhage/necrosis (adults)–> explosive dysentery, decreased milk production
Bovine Coronavirus respiratory infection
Mild dz- coughing and rhinitis
More severe- pneumonia in 2-6 m.o. calves
Part of shipping fever complex
Cattle arriving at feedlot w/ high BoCV Ab titer are less likely to contract/spread dz
Found in URT and LRT
Transmissible gastroenteritis virus (TGEV)
pathogenesis, reasons it targets young animals
= highly contagious coronavirus w/ severe clinical signs in piglets
- Feco-oral transmission–> mature enterocytes of SI–> vomiting, watery diarrhea, weight loss, dehydration, death w/in days
Young more susceptible b/c less gastric acid and milk diet protect virus in GIT, slower turnover of enterocytes than adults, immature immune system, more vulnerable to electrolyte/fluid loss than adults
Porcine respiratory coronavirus
Variant of TGEV w/ partial deletion of S protein gene–> altered tropism (strong cross-immunity to TGEV)
Aerosols–> mild to no respiratory signs
Porcine epidemic diarrhea virus (PEDV)
Clinically/pathogenically similar to TGEV, but different Ag/genome/serological properties
Porcine hemagglutinating encephalomyelitis virus (PHEV)
Aerosol transmission–> primary replication in nasal mucosa/tonsils/lung/SI–> CNS via peripheral nerves–> vagal sensory ganglia/gastric myenteric plexus–> vomiting/wasting dz in piglets (<3 w.o.)
Passive protection from maternal Ab
Canine coronavirus
Enteric dz: worldwide in domestic & wild dogs, single serotype, similar path. to other spp.
Resp. dz: associated w/ “kennel cough” complex
- genetically distinct from enteric virus
- aerosol spread–> mild dz- dyspnea, pneumonia, occasionally death
Feline coronavirus
2 biotypes
2 biotypes of same virus (only difference is dz induced):
1) Feline enteric coronavirus (FECV)- mild enteric disease
2) Feline infectious peritonitis (FIP)- fatal systemic pyogranulomatous dz
FIP
clinical signs and 2 forms
Clinical signs depend on vasculitis and extent of organ damage from loss of blood supply
Wet form: many vessels affected–> exudation into body cavities–> viscous/clear ascites–> abdominal dissension/thoracic effusion
Dry form: signs vary depending on which organs damaged by granulomas
Both forms: white/grey nodules around vessel walls in omentum, liver, peritoneum, etc.
FIP
pathogenesis
Virulent mutant emerges with strong tropism for macrophages and monocytes–> productive infection–> perivascular aggregations–> macrophage activation and release of inflamm. mediators–> increased vascular permeability and chemotaxis–> further inflamm. cascade
Kittens prone as maternal Ab wanes, other Ab not protective
Likely maintained in population by sub-clinically shedding cats
Poultry coronavirus
pathogenesis
= infectious bronchitis virus
- Respiratory +/- systemic dz of chickens spread via aerosols and fecal-contaminated feed
- ciliated resp. cell infection–> viremia (18-48 hour incubation)–> damage to URT/LRT +/- ovary, kidney, oviduct
1-4 week old chicks:
- virulent strain- gasping, coughing, dyspnea, mortality 25-30% (up to 75%)
- less virulent strain- milder signs, lower morbidity/mortality
Laying hens- decreased productivity
Poultry coronavirus
control and diagnosis
Both Ab and CMI required for protection- vaccinate 1-day chicks extensively
- can have vaccine breaks when poor match to endemic serotype
Dx: sample tissues, RT-PCR
Lyssavirus genotype I (Rabies) epidemiology
Worldwide except Japan, UK, Australia, NZ, Antarctica, parts of Europe
Maintained in given region within particular mammalian host in 1 of 2 cycles:
1) Urban rabies in dogs (dog population > 4.5 dogs/km^2)
2) Sylvatic (wildlife)- in US 36.5% in raccoons, 23.5% in skunks, 23.2% in bats
Lyssavirus genotype I (Rabies) pathogenesis
Transmission primarily through bites (saliva)
- -> replicates in local muscle cells
- -> variable incubation (weeks-years)
- -> binds ACh receptors @ NMJ
- -> climbs peripheral nerves to CNS via retrograde axonal transport
- -> up spinal cord to brain
- -> lymbic system (loss of behavioral ctrl = “Furious” rabies)
- -> neocortex (“Dumb” rabies)
- -> centrifugal spread down nerves to non-nervous tissue (e.g. salivary glands)
- -> death due to respiratory depression
Lyssavirus genotype I (Rabies) control
1 vaccine (inactivated or attenuated) prevents disease from all strains In areas with epidemic urban rabies in dogs vaccination (+/- spay/neuter) >>> culling Vaccination coverage must be 60-80% of dog population to significantly reduce risk in local human populations
Vesicular stomatitis
Pathogenesis, clinical signs, similar dz
- Febrile dz of horse, cattle, pig (exotic to Australia)
- Clinically indistinguishable from FMD- main difference being that horses can get infected
- Mechanically transmitted by arthropod vectors (black flies)
- Vesicular lesions on oral mucosa, teats, coronary band, snout, tongue for 7-10 days
Bovine Ephemeral Fever (BEF) epidemiology
- Arbovirus spread by Culicoides and mosquitos
- Outbreaks follow conditions favorable for vectors
- Tropics: outbreak after rainfall
- Temperate: outbreaks in summer
- High morbidity, low mortality
Bovine Ephemeral Fever (BEF) pathogenesis
Transmission via Culicoides or mosquito
- -> primary site of replication unknown
- -> 3-4 day viremia, 4-7 day incubation
- -> sudden onset fever, decreased milk production, depression, lameness, recumbency
- associated w/ neutrophilic, polyserositis & hypocalcemia, neutralizing Ab (day 3 of clinical signs)
- -> recover w/in 3 days
- -> strong immunity post-infection
Bovine Ephemeral Fever (BEF) diagnosis and treatment
Dx: typical clinical signs (affecting majority of herd)
Tx: anti-inflammatory drugs effective, inactivated vaccine available
Bunyavirus Akabane
epidemiology
- Arbovirus spread by Culicoides brevitarsis and mosquitos in tropics/subtropics of Middle East, Asia, Australia, and Africa
- Sporadic epidemics correspond to vector movement
- Infects sheep and cattle (+ goats and deer)
Bunyavirus Akabane
pathogenesis
Susceptible dam bitten by infected vector
- ->crosses placenta w/o causing disease in mother
- ->variable signs in fetus depending on stage of development
- Primary fetal infection = encephalomyelitis, polymyositis
- Survivors have cerebral cavitations, hydranencephaly, arthrogryposis, torticolis/scoliosis/kyphosis
Bunyavirus Akabane
diagnosis and prevention
Dx: usually by gross pathological findings, serological findings (neutralizing Ab fetal/newborn sample, paired maternal sera)
Inactivated vaccine available in Japan and Australia
Family Paramyxoviridae
2 major glycoprotein peplomers
1) Hemagglutinin/Neuraminidase (H/N) protein- involved in attachment
- Neutralizing Ab directed against HN
2) Fusion (F) protein- cleavage essential for infectivity (esp. Newcastle Disease)
- (similarly, G protein in Hendra and Nipah viruses necessary to infect)
Avian paramyxovirus 1 (Newcastle Disease- NDV)
epidemiology
- Highly contagious resp/GI/neural dz in poultry worldwide
- Varying virulence and tropism between strains
- Many avian species susceptible (turkeys, pigeons, chickens, etc.); wild birds = reservoir
- Excreted in feces or respiratory tract, persist in environment or carcass for weeks, transmit via aerosols or contaminated feed/water
Newcastle Disease Virus
pathogenesis
Feco-oral or aerosol transmission
- -> replicates in respiratory or GI epithelium
- ->primary viremia
- ->spleen and bone marrow
- ->secondary viremia
- -> lungs, intestines, CNS
- -> (5-day incubation) clinical signs depend on strain virulence, tissue tropism, host factors
Newcastle Disease Virus
virulence of strains and associated clinical signs
- Velogenic = high virulence–> sudden high mortality (~100%)
- Mesogenic = intermediate–> mild dz (coughing, production losses), mortality only in young
- Lentogenic = mild dz or inapparent infection (F protein only cleaved in RT or GIT)
- virulence associated w/ cleavability/activation of F protein in different tissues
- Viscerotropic vs. neurotropic
- viscerotropic velogenic isolates: severe fatal dz w/ intestinal hemorrhage & bright green diarrhea
- neurotropic velogenic: respiratory signs–> neurological signs (tremors, paralysis)
Newcastle Disease Virus
diagnosis and control
Dx: virus isolation from swabs in embryonate eggs, HA/HAI
Pathogenicity test: mean death time for eggs, sequence F protein, RT-PCR
Ctrl:
- NDV-free countries: test and slaughter
- NDV-endemic countries: attenuated live vaccination strains
Morbillivirus Rinderpest
epidemiology
= “cattle plague” (eradicated in 2011)
- Acute fatal dz w/ pyrexia, inflammation, necrosis of mucous membranes
- High morbidity, high mortality
- 1 serotype, different strains (one vaccination protects against all strains)
- Virus shed in feces, urine, respiratory secretions (often before clinical signs)
- Labile in environment (requires close contact)
- No carrier state (difference from FMD)
Morbillivirus Rinderpest
pathogenesis
Transmission by inhalation
- ->replication in tonsils and local URT lymph nodes
- ->viremia
- ->other lymphoid tissue, respiratory/GIT mucosae
- -> leukopenia from lymphoid necrosis
Morbillivirus Rinderpest clinical signs (progression)
3-5 day incubation–> rapid pyrexia (prodromal phase)
- ->mucosal phase (necrotic foci in nasal, oral, urogenital mucosa) = mucopurulent nasal/ocular discharge
- -> necrotic foci–> erosions (fever regresses when ulcers appear)
- -> hemorrhagic diarrhea
- -> death w/in 12 days (dehydration, wasting, etc)
Rinderpest
diagnosis and control
Dx: viral Ag in spleen, lymph nodes, or secretions
Ctr: quarantine, widespread attenuated vaccination (–>eradication in 2011)
Pest de Petit Ruminants
= “goat plague” in Africa
- acute, contagious dz in small ruminants
- spread by aerosols, direct contact
- similar signs to rinderpest, up to 70% mortality
- ctrl with rinderpest vaccine (PPRV vax now also available)
Morbillivirus Canine Distemper
epidemiology
- highly contagious dz of dogs/carnivores worldwide
- outbreaks in dogs, foxes, skunks, raccoons, ferrets, lions
- labile in environment- aerosol or direct contact transmission
- urban dogs: young dogs as maternal Ab wanes (maintained in population through infecting susceptible animals)
- rural dogs: lower population pressure, more unvaccinated dogs–> outbreaks among various ages
Canine distemper
pathogenesis
Transmission via aerosols or direct contact
- ->initial replication in URT
- ->lymphocyte-associated viremia
- ->reticuloendothelial system
- ->secondary viremia
- ->mucosal epithelium of GIT, RT, CNS (neurons & glia)
- ->incubates 3-6 days
- ->dz of variable severity/duration
Canine distemper
clinical signs
- incubates 3-6 days
- biphasic pyrexia- 2nd peak w/ oculonasal discharge, pharyngitis, tonsillar enlargement
- +/-skin rash & pustules
- hyperkeratosis of nose & footpads
- acute: cough, vomiting, diarrhea; followed by either recovery or –>
- CNS dz: (grave prognosis) myoclonic contractions, ataxia, paresis, seizures, often death
Canine distemper
diagnosis and control
Dx: presumptive, IHC on smears from discharges
Vaccination (part of C3) effective as maternal Ab wanes
Hendra virus epidemiology
- acute respiratory dz, sporadic outbreaks in horses (+/-humans) in NE Australia since 1994 (usually late winter/spring)
- reservoir = pteroid flying fox fruit bats (Pteropus alecto, P. conspicillatus)
- seroprevalence 2-50% in bat colonies (suggests non-lethal to bats)
- 80% case fatality rate in horses, 57% in humans
Hendra virus
clinical signs/findings
- similar signs to African Horse Sickness: horses tachypneic, tachycardia, ataxic, frothy nasal discharge, collapse (many die in 12-24 hours)
- congested, firm, fluid-filled lungs w/ dilated lymphatics, thick/foamy/bloody exudate in airway
- other possible signs: shifting weight/uneasiness, neurological signs, congested mucous membranes, weakness
Hendra virus control
Killed/inactivated vaccine available for horses (boosters and adjuvants required)
Ab-mediated response
Vaccinating horses important for human safety (all human cases associated with contact with infected horses)
Equine Viral arteritis
epidemiology
- Worldwide
- Usually asymptomatic (rare clinical outbreaks- mostly in trotters and pacers)
- Susceptibility: horses > mules > donkeys
- SBs more seropositive than TBs
- Transmission via respiratory tract (aerosols), genital tract (35% of infected stallions shed in semen), transplacentally
Equine viral arteritis
clinical signs
3-14 day incubation–>
fever, excessive lacrimation, conjunctivitis, rhinitis, nasal discharge, stiff gait, ventral edema, urticaria on head/neck, abortion
- worse in very young and very old
Equine viral arteritis
pathogenesis
Aerosols
–>replication in alveolar macrophages
–>bronchial lymph nodes
–>viremia (free and macrophage-associated)
–>primary targets = macrophages & endothelium
(–>edema, congestion, etc.)
–>secondary targets = kidneys, liver, seminiferous tubules (carrier stallions= reservoir), etc.
–>after acute infection virus eliminated from mares, geldings, and 65% of stallions
- abortions follow viremia and transplacental spread
Equine viral arteritis
diagnosis and control
Dx: RT-PCR, virus isolation from semen or respiratory secretions, serology (ELISA, neutralization)
Vaccine available
Porcine Respiratory and Reproductive Syndrome Virus (PRRSV)
clinical signs and dz processes
- reproductive failure in sows
- pneumonia in young pigs- respiratory distress and cyanosis of skin (ears, vulva, etc.) exacerbated by Mycoplasma spp. or Streptococcus suis infection
Porcine Respiratory and Reproductive Syndrome Virus (PRRSV)
epidemiology, diagnosis, control
- exotic to Australia (North America and Europe only)
- infects pigs only
- Dx: serology (ELISA, neutralization) or isolation
- Ctrl: quarantine, vaccination
Infectious bursal dz of chickens (IBDV)
epidemiology
- Worldwide
- In naive flock morbidity up to 100%, mortality up to 90% (20-30% in endemic flocks)
- Usually infects 3-6 week-old chicks
- No effective vaccine
- Very stable in environment- resistant to detergents and disinfection
Infectious bursal dz of chickens (IBDV)
pathogenesis
Feco-oral transmission
- -> replicates in gut-associated macrophages
- -> portal system
- -> viremia
- -> preferential location in bursal lymphoid cells (destruction of Bursa of Fabricius–> immunodeficiency)
- -> excreted in feces (highly contagious)
Vesivirus: Vesicular exanthema of swine
- eradicated in 1956
- clinically indistinguishable from FMD
- Lab Dx essential- isolate from vesicles
- closely related to San Miguel Sea Lion Virus (swill?)
3 diseases with same clinical presentation as FMD:
- Vesicular stomatitis- difference = seen in horses
- Swine vesicular dz (picornaviridae- enterovirus)
- Vesicular exanthema of swine (eradicated in 1956)
Agents that cause feline URT dz
Feline herpesvirus
Feline calicivirus
Chlamidophyla
Feline calicivirus
epidemiology
- URT pathogen in large/domestic cats
- all ages susceptible but most common in kittens 2-6 m.o. (maternal Ab)
- large titers of virus remain in oronasal secretions for months-years
- persistent infection possible post-recovery or sub-clinical infection
- maintained in population in small proportion of infected animals (not in latency)
Feline calicivirus
pathogenesis
Transmission by aerosol or direct contact via oronasal or ocular routes
- -> rapid spread through URT/conjunctiva
- -> transient viremia
- -> variable clinical signs (dependent on strain virulence)
Feline calicivirus
clinical signs
Incubates ~5 days
- -> conjunctivitis, rhinitis, tracheitis, pneumonia
- -> gesticulation & ulceration of tongue/oral mucosa, shifting lameness
Feline calicivirus
diagnosis and control
Dx: RT-PCR on swab material, paired sera
Ctrl: inactivated & attenuated (not if pregnant or immunocompromised) vaccines available
Feline core 3 vaccines
Feline herpesvirus
Feline calicivirus
Feline panleukemia
Rabbit hemorrhagic dz
epidemiology
- Highly contagious/potentially fatal dz in European rabbits (>2 m.o.)
- Virus shed in excretions, persists in environment
- Transmission: deco-oral, inhalation, conjunctiva, mechanical (fleas, mosquitos, etc.)
- Similar to myxomatosis, except contagious
- High morbidity, high mortality
Rabbit hemorrhagic dz
pathogenesis and clinical signs
Replicates in mononuclear phagocytic cells
- -> acute hepatic necrosis, DIC
- -> 3-day incubation
- -> fever, depression, dyspnea, serosanguineous nasal discharge, hematuria, neurological signs
- -> death w/in 36 hours of onset of clinical signs
Rabbit hemorrhagic dz
diagnosis and prevention
Dx: many dead rabbits w/ characteristic gross lesions; RT-PCR
Inactivated vaccination available (may cause local alopecia)
Scrapie prion hypothesis
Scrapie = variant of host’s PrP protein (PrPsc) that alters host PrP structure
–>takes on structure of infectious prion
–>prion propagated through altered protein folding (misfolded protein unable to be degraded–>accumulates)
Support for hypothesis:
- no nucleic acid structure IDed so far
- deletion of PrP gene in mice protects against Scrapie
- protease-resistant PrPsc demonstrated to alter PrP conformation in vitro
Scrapie pathogenesis
Likely horizontal (+ iatrogenic) spread of unknown mechanism
- -> agent first appears in tonsils, spleen, lymph nodes (likely after replication in follicular DCs)
- -> 3-5 year incubation while it spreads to/through CNS
- -> lipid- (myelin-) associated infection resulting in deposition of rods/fibrils (scrapie associated fibrils- SAFs) in brain
- vacuolation and degeneration of CNS neurons, astrocyte hypertrophy
Scrapie epidemiology
- likely horizontal (+ iatrogenic) spread)
- may be significant population of sub-clinically infected sheep resistant to clinical dz
- PrPsc found in macrophages of mammary tissue during mastitis- suggestive of transmammary transmission
Scrapie diagnosis and control
Dx: not cultivable or detectable other than by animal inoculation (only possible with some strains)
- usually diagnosed based on histopathology
Ctrl: only successfully eradicated from NZ and Australia by aggressive slaughter campaigns and quarantine/import regulations from endemic areas
Bovine Spongiform Encephalopathy (BSE)
pathogenesis and dz characteristics
Cattle likely infected via contaminated feed (most cases related to ingestion of meat meal)
- -> incubates for several years
- -> hyperesthesia, apprehension/nervousness, frenzy
- -> ataxia
- -> debility, recumbency, death (wks-mos)
- spongiform lesions found in brains
- concurrent natural SEs seen in felid spp. and some zoo antelope
- agent may be scrapie or some other amplified agent normally found in low levels in cattle
BSE epidemiology
- Primarily occurred in British dairy cattle after changes in meat processing protocols (decreased temperature and lipid solvents used during processing–> reduced inactivation of scrapie-like agents)
- Most cases related to ingestion of meat meal
- Dramatic reduction in cases since 1988 ban on feeding meat meal to animals
- Recently new strain has arisen- Bovine Amyloidotic Spongiform Encephalopathy (BASE)- assoc. w/ amyloid plaque deposition
BSE diagnosis and ctrl
Dx: histopathology of brain through foramen magnum
- PrP detection w/ ELISA
Ctrl: ban on feeding meat meal to animals since 1988
Transmissible Mink Encephalopathy
- prevalent in mink farms in US
- possibly from feeding them scrapie-infected sheep or BSE-infected cows
Chronic wasting dz (TSE)
- mule deer, white-tailed deer, Rocky Mountain elk in US
- progressive weight loss, behavioral changes, salivation, PU/PD
- infectivity found in muscle- potential risk of eating infected venison
Kuru (TSE)
- progressive paralysis in Fore people (mostly women and children) of New Guinea
- association with ritual cannibalism of dead relatives
- women and children eat viscera (higher dose)
Creutzfeldt-Jacob Dz (CJD)
Rare presenile demential in humans 3 epidemiological patterns: - familial - sporadic - iatrogenic- GH administration from pooled pituitary glands, instrument contamination
BSE zoonotic potential
- no increased risk in farmers
- affected people have specific polymorphism in PrP gene (encoding methionine residue @ position 129)
- ~80 cases SE per year in UK (~1/4 due to CJD)
