Foundations exam 4

Retroviruses

the virus attaches to a host cell and enters and uses reverse transcriptase to turn its RNA into DNA. It then uses integrase to insert the viral DNA into the host’s DNA

Retroviruses induce cancer by

intergrating their genetic material into host cell DNA, introducign viral oncogenes, or altering the expression of normal host genes
transducing viruses have a high chance of forming tumors

Acute transducing viruses

pick up host protooncogenes and turn them into overactive cancer causing genes (v-onc genes) inside their own viral genome
they cause rapid tumor grwoth after a very short latent period because the vrial genome drives constant cell division

Felines sacroma virus (FeSV) requires

FeLV - the helper

Becuase expression of v-onc is controlled by the vitrus ___% of host cells infected will become transformed

100%

Provirus

the dna form of the retrovirus genome which integrates into the host cell chromosome

Chronic non-transducing viruses

integrates near a host proto-oncogene which can inappropriately activate the gene and cuase transformation
intergration into the genome is a random event and may infect for years without causing cancer
FeLV

FeLV are 60x moe likely to develop

Lymphoma

Proviruses can act as _____ or _____ of proto-oncogene expression

promoters or enhancers

Long latent non-transducing vrisues

reetroviral protein is actually responsible for cell transformation

Bovine leukemia virus causes what cancer and how

long latent non-transducing viruses
B cell lymphoma or lymphosacroma caused by tax protein

Jaagsiekte sheep retrovirus causes what cancer by what

Long latent non-transducing viruses
pulmonary adenocarcinomas cuased by gag protein

BLV tax protein how does it cause cnacer

is a transcritptional activatro and turns on host genes in cell cylce, inhibitis apoptosis so infected cells survive longer than normal, interferes with cellular DNA damage response, increasing cellular mutations
favors longer-lived cells that also are activated to divide fequently
leukemia/lymphoma doesn’t devlop until 4-8 years and only 1-5% will develop cancer

FeLV contains a viral capsid made of rptoein

p27 and this is the protein detected in virus antigen test

FeLV -A

contagious and passed horizontally from cat to cat
other subgroups evolve de novo in FeLV-A infected cat by mutation or recombination
pathogenicity of FeLV -b nad FeLV-c is higher

FeLV -b

commonly associated with malignancies such as mediastinal lymphoma and also occurs in multicentric lymphoma

FeLV-C

associated with pure red cell aplasia
recpotr interaction blocks the differentation of erythroid progenitors
severe anemia nad macrocytosis without reticulocytes

FeLV transmission

infected cats shed virus within 30 days of exposure
shed in saliva and less commonly shed in nassal secretions, milk, urine, or feces
transmitted mainly in oral nasal route ad less commonly via bit wounds
horizontal - cats that live together or fight
vetrically and horizontally - infected queens to kittnes
kittens more susceptible to becoming progressively infected than adult cats

FeLV infection outcome depends on

virus strain, challenge dose, route of inoculation, host immune function (age, genetic, co-infections, stress, immunosuppressive drugs)

Progressive FeLV - s/s

anemia, immunosuppresion, secondary infections, neoplasia, immune mediated disease, FeLV-associated neuropathy, repro disorders

FeLV - secndary problms

periodontal disease ad gingivitis (FIV mainly), chronic bacterial skin and ear infection, URTI, parasites, lymphoma, leukemia, squamous cell carcinomas, immune mediated disorders, myelodysplastic syndrome

Cats with wavy whiskers mean

there is a 89.3% chance that cat has feline leukemia virus

FeLV - antigen testing

postive 30+ days after exposure, aboritve infection, negative on POC test, regressive infection negative or psotive

FeLV - confirmatory testing

ideal and may include a differnt manufauters POC test, PCR, or IFA

What FelV clincial stage has a reduced lifespan

progresive

Proviral FeLV progresive infections are commonly associated with

high levles of proviral DNA and antigen positive test while low levesl are associated with regressive

FeLV - prognosis

high psotive ~1.37 years
low psotive were still alvie

FeLV treatment

no cure
symptomatic, glucocorticoids and other immunosuppresive drugs should be avoided unless imunne mediate cytopenias
interferons often used but efficacy is not proven
antivirals - safety ad efficacy not really proven

FeLV managemnt

parasite control up to date, detailed PE and CBC every 6 months
serum biochem and UA annually
feed a complete and balanced diet and avoid raw meat or unpasteurized dairy products
maintain vx status and should remain up to date on core vx (yearly due to protection may be incomplete)

What FelV cats can shed

only viremia (antigen positive)

When if FeLV a core vaccine

kittens

RNA particle technology and dendritic cels

vx is composed of an outer protein shell that make sdendrites recongize it for the fuutre

Dendritic cells

msot potent antigen presenting cells, ability to activate t cells directly and promote B cell activation
cellular and humoral (antibody) imunity

FIV transmission

shed 14 days of esposure in saliva
horizontally - bite wound and FIV infected WBC
Transmission from queens to kittens or cohabitating without fighting or sexually is uncommon unnatural infection

FIV antibody testing

postive 60+ dyas post infection
materal antibodies may take up to 6 months to clearF

FIV confirmatory testing

differnt manufacture’s POC test, PCR, or a western blot test

FIV treatment

supportive tx, dental prophylaxis, systemic glucocroticoide if necessary (increased plasma viremia) drbepoetin if anemai, topica lactoferrin for stomattits
antivrials - zidovudine, fozivudine, human recombints IFN-alpha

Equine Infectious Anemia - is it reportable and s/s and dx

is reportable
s/s - fever, depression, anemia, edema, muscle weakness, weight loss
dx - coggins

How can viruses cuase diarrhea

Infection of villus cells can affect absorption (loss of absorptive intetinal epithelial cells at tip fo villus means less lactase acivity which leads to malabsorption and osmoic diarrhea, villus blunting)
infection of crypt cells can block regenr of the villus (villus collapse cauign mucosal ulceration and loss of the epithelial barrier and this can lead to sepsis and leakage of blood and plasma proteins into the intestinal lumen causing hemorrhagic diarrhea

What viruses infect the villus cells

Feline/canine/bovine/equine coronavirus, canine, bovine, equine rotavirus

what viruses infect the crypt cells

Feline panleukopenia virus, canine parvovirus type 2
bovine/equine coronavirus

Feline panleukopenia - taxonomy, species, genome, nake virus

parvovirdae, genus parvovirus, felidae, ssDNA, highly stable

Feline panleukopenia - transmssion, inactivation

transmission - formites, short shedding+ long persistnce, in utero, direct contact, fecal-oral
inactivaiton - bleach, heat, formaldehyde (not 70% alcohol)

Feline panleukopenia - relies on what to replicate

host cell polymerase in cells undergoing cell division

Feline panleukopenia -where does it go in the host

Adult - lymph, bone marrow, intestinal crypts
prenatal, neonatal - lymph, bone marrow, CNS (cerebrum, cerebellum, retina, optic nerves), myocardium

Feline panleukopenia - systemic infection

Intranasal or oral infection → oropharynx lymphoid tissues (18-24h), viremia (2-7dpi), dissemination

Feline panleukopenia - in utero

early - fetal death, infertitily, abortion, mummified fetuses
late/neonatal - CNS tissue development, cerebellar hypoplasia, litter mate differences

Feline panleukopenia - s/s

Systemic infection, lymphoid depletion and thymic involution, GI replication, myocarditis and cardiomyopathy,, fetal death, CNS disease, co infections,
Acute, self limigting - fever, depression, vomiting, anorexia ± diarrhea→ dehydration
thickened intestinal loops mesenteric lymphadenopathy
BM suppresion

Feline panleukopenia - dx

Blood work - intial neutriphilia from gut infection, lymphopenia ± thrombocytopenia
seroloy - serum neutraliztion, titer, protective levles/exposure (single), Active infection (4 fold increase), HI (pig erythrocytes)
fecal viral antigen - low (24-48hr) hsedding periods, not approved by manufactures
PCR - feces, saliva, urine (kittens)

Feline panleukopenia - tx, prevention

tx - supportive care (fluids, nutritional support, antiemetics, ± abc) isolation
prevention - vx, decontamination, decreased prevalence, life long immunity suspected follwing infection

Canine parvo - virus properties

non-enveloped, DNA virus, single stranded
small genome only about 2% different from feline panleukopenia virus

Canine parvo - pathogeneis

crypt damage leads to decrease secretions and decrease absorption and icnreased permeability

Canine parvo - signalemtn

any breed, age, or sex
Puppies - 6 weeks to 6 months old
increased risk - rottie dobies, labs, american stffodshire terriers, german shephers, english springer spaniel, alaskan sled dogs

Canine parvo - s/

Vomiting, diarrhea (foul smelling, mucoid→ melena/hematochezia), anorexia, fever, lehargy, sudden death (sepsis, disseminated intravascular coagulation)
cutaneous lesions (uncomon), seizures (uncommon and due to cerebellar hypoplasia with in utero infection is rare)

Herpesviruses - type of virus, transmssion, pattern of infection

virus - enveloped, dsDNA virus
transmission - fomites and respiraotry spread
pattern of infection - causes acute infeciton but can induce latency in long lived cells

Herpesviruses - tx adn prevention

tx - antivirals (oral or topical), supprotive
prevention - some Vx available, low stress envrionment, avoid contact with infected animals, wash and disinfect

Bovine herpes virus -1 cuases what disease, geographic range, morbodity/mortalitly, host/reservoir

infectious bovine rhinotracheitis virus (IBR), red nose
range - world wide
morbidity/mortality - may be up to 100% /1-% mortality
host/reservoir - latently infected cattled (may shed) - mjoar problem in feedlots and dairies

Bovine herpes virus s/s

rhinotracheitits - respiraotyr form of the disease
genital disease - pustular vulvovaginitis and balanopostitis
aboriton - over 4 mo, embryonic death, oophoriits, CL necrosiis
encephalitis - neurologic signs, less common
may cuase a systemic disease in newborns

Bovien herpes virus - vx

often combo, goal develop immunity at youngest age possible, vx early (4-6 weeks)
3 types - killed (safer for pregnant cows, may not provide long-lasting immunity), MLV (parenteral) - may cuase abortions, MLLV (intrasal) - prevent interference of maternal antibodies

Canine herpes virus puppies - transmission, tx, prevention

transmssion - mother to pup during birth or in older animlas direct contact with virus contiang fluids (nose, mouth vaginal)
tx - moving the litter to nurse from a mother with antibodies, keeping them warm
prevention - avoid contact with infected animals, wash and disinfect

Canine herpes virus (CHV) Puppies - s/s

young puppies under 3 weeks
death within 48hrs of symptoms
diarrhea, anorexia, hypothermia, poor febrile response, unchecked replication and systemic spread
fatal generalized necrotixing nad hemorrhagic disease

Canine herpes virus (CHV) - older puppies and adults

respiraotry, ocular, or genital tract
no systemic spread
generally subclinical or mild and self limiting
short replication periods
latency in nervous/nervous
reactivation with immunosuppression adn stress
eneally see conjunctivitis, increased nasal secretions, genital lesion
can see kennel cough

Feline herpes virus - s/s

fever, tearing, rhinitis, salviation, dperession, anorexia
ocular - conjunctivitis, keratitis, dendritic ulcers (pathogonomonic)

Feline herpes virus - tx, prevention

tx - antivirals (oral or topical), supportive, famclovoir, clodfovir, intranassal vaccines may lessen disease in some cats
prevention - vx (FVRCP), low stress environment, avoid contact with infected animals, wash and disinfect

Felinc calicivirus - s/s, transmission

s/s - feverm rhiniits, oral and upper respriatory signs - lungual ulceration, feline chronic gingivostamatitis, limping syndrome, virulent systemic feline calicivirus infection, supportive tx
transmssion - fomites, aerosols

only give cats antibiotics for URT infections if they are

fever, lethary, or anorexia is present concurrentyl with mucopurulent nasal discharge
first line - doxycyline or amoxicillin

Canine adenovirus -1 - type of vrius, hosts, transmission

non-enveloped DNA virus
hosts - dogs, ottters, ferrets, ears, foxes, wolves
transmission - oronasal exposure to saliva, feces and urine - fomites also possible

canine adenovrirus -1 s/s

early - fever depresison, leathary
blue eye apperance of the cornea
jaundice is not reliable incread use hepatic damage on Chem panels (increase ALT and AST)
luekponeia and proteinuria
abdoimnal discomfort, pale MM< tonsillar inflammation, petechia of oral mucosa, and hemorrhage
vomiting and diarrhea possibel with hematemeisis
CNS sigsn due to heptic encephalopathy or CNS inflitations
increased clotting times

what cuases blue eye in cnine adenovirus -1

Type III hypersensitiivty
immune complex deposition after infection of corneal endothelial cells
will see corneal edema, anterior uveitis and secondary glacucoma
can be unilateral but often develops bilaterally
do NOT give Cav-1 in vaccines and ely on CAV-2 for cross protective immunity

CAV-1 - dx

PCR of oculuar, nasal, or pharyngeal swabs/tissue → sensitivie and specific (can differentiate between 1 and 2)
serology through IFA → cannot differentiate between 1 and 2
virus isolation
post mortem → centriobular hepatic necrosis with viral inclususions bodies, microhemorhages, gallbladder edema

CAV-1 - tx and preveiton

tx - supportive care - iv fluids, blood product administation, lactulose (hepatic encephalopathy), steroids/NSAIDS for blue eye
prevention - MLV vx, belach, hydrogen peroxide

CAV-2 - type of virus, binds to what cells, increased risk of,

doubsle stranded, non-enveloped DNA virus
binds to epithelium of upper respiraotyr tract, bronchi, alveoli and lymph nodes
intitial viral injury icnrease risk of secondary bacterial co pathogens → penumonia is the most common

Paramyxoviruses and pneumoviruses - type of virus, transmission, tx, pattern of infection, prevention

virus - enveloped, negative sense RNA virus
transmission - respiraotyr pathogen, close contact
tx - supportive
pattern - some acute infection in respiraotyr tract, other acute systemic infection (occ focal persistence)
prevention - vx, avoid contact, wash and disinfect

Canine distemper virus - type of virus, transmission, host range

virus - morbillivurus, enveloped, negative-sense RNA
transmission - respiraotry pathogen, close contact
host range - carnivores, dogs, ferrets, otters, seals, skunks

Canine distemper - s/s

diphasic fever, depression, anorexia
serious - interstitial pneumonia → bronchointerstitial/bronchopneumonia due to secondary bacterial infeciton, vomiting, diarrhea, pustular dermaitits (rare), seizure,s cerebellar or vestibullar signs, para/tetraparesis, myocolonus, anterior uveitits, blindness, death
neurologic s/s vary with segmetn of nervous system

Canine idstemper virus - pathogensis

1) aerosol droplets contact upper repsirtoary tract epithelium
2) infects adn multiples in tissue macrophags
3) migration to tonsils and bonchial LN
4) repication in lymphoctes
5) dissemination ot other lymphoid organs
6) depending on host’s immune repsonse - infection of epithelium in respiraotry tract, gi, urogenital OR infection of brian (encephalitis)

Canine distemper virus - outcome depdnet on humoral and cell mediated immunity

Adequat - celar virus, no s/s
Intermeidate - eptihelial tisuse, may resovle if antboidy titiers increase, may persit in brian/mucosal epithelium
inadequat - spreads to many tissues, dramatic, severe clincial signs (bacterial infecitons complicate clinical illness, virus persists in tissues until death

Bovine respiraotry syncytial virus (BRSV) - distributiuon, affects waht cows, transmission

worldwide
young beef and diary cattle - subclincial in adults but shed to younger
transmssion - aerosol or direct contact

Bovine respiraotyr syncytical virus - localized to where, predisposes to what, compare to other BRDC viruses,

localized repsiraotry (lower tract) and predisposes to 2nd bacterial pneumonia
diffuse interstitial pneumonia with edema - most severe pathology of BRDC
necrotizin bronchiolotis

Bovine respiraotyr sycytial virus - s/s

high fever, open mouthed breathing, depression and dereased feed intake, intersitial penumona dn edema, increase RR, cought and dyspnea

BRSV dx, tx, and prevention

dx - nasal swab or lung tissues, PCR or virus isolaiton, serology
tx - supportive care
vx - MLV killed
biosecruity, low stress, adequate nutrtion

Parainfluenza virus type 3 - transmisison, presenation

transmisison - aerosal or direct contact
presentation - mcalves 2-8 months, least virulent

FIP pathogeneis

FECV pases through intestinal tract and invade and replicate in columnar epithelial cells, transform to meesenteric lymph nodes and replicate in marcophages and mutation that leads to systemic infeciton (FIP)

Feline coronavirus - serotype I

highly dominant worldwide, accounting for roughly 80-90% of all feline coronavirus infections and natrual FIP cases globally

Feline coronavirus - serotype II

less common in natrual field infections, though its prevalence varies by region, formed via historic recombination events with canine cornavrius

risk factors for FIP

under 2 years, host genetics and immunity, immunosuppresion from stressful events or concernt infections, purebred cats

FIP - s/s

Neuro - meningitis, seizures, ataxia, hyperesthesia
ocular - anteiror/posterior uveitits, panuveitis, iris color change, retinal hemorrhage
cardio - vasculitis, myocardiits, epicadiits, pericardial effusion
dermatologic - fragile skin syndrome, papular lesion, pyogranulomatous dermaittis
repro -orchitits, testicular swelling
abdominal - intestinal mases, lymphadenitis, perioniits with effusion, renal granulomas
respiratory - pleural effion, pleuritis, penumonia, rhinits

FIP - dx

no single test is definitive
hx, pe
blood - non-regenerative anemia, lymphopenia, hyperglobulinemia, low albumin:globulin ratio
pocus - detect effusion, organ hcanges, help guide samples
u/s - assess effusion, organ lesions (liver kidneys, lymph nodes)
x-rays - effusion, organomegaly, masses, thoracic changes
FNA/cytology, fluid analysis, histology, PCR< immunostaining, rule out, tx respose

FIP intial - dx (CBC, Chem)

Nonregen anemia (lyphopenia, neutrophilia)
hyperglobulinemia, hypoalbuminemia, low A:G ratio (values over 0.4 makes FIP highly likely)
hyperbilirubinemia
increased liver enzyme
serology not helpful
survivial correlation - worse with increased bilirubin and lactate dehydrogenases

FIP - fluid analysis/cytology, RT-PCR< histopathology and IHC

fluid analysis and cytology - in effusive cases, fluid is typically high in protien and low in cellulalrity
RT-PCR - high specificty, less sensitive in blood due to low or transient viremia
histopathology and IHC - the definitve dx refernce test
ID pathognomonic pyogranulomatous inflammatio and directl visualizes viral antigen in macrophages

RT -PCR -FIP

detecting FCoV (not FIP)
high specificty
feces - cats shedidng virus (does not aid in dx of FIP)
qunatiative PCR - cycle threshold low number =lot of virus, corssing point high nmber = lot of virus

FIP - tx

Nucleotdie/nucleoside analogues
protease inhibitors
usually improve within few days (48-72 hours) do not treat for weeks if no improvemnt
very few adeverse events but monitory is still requireds -BW uroliths, pruitis

Urolithiasis - cuased by what FIP rx

Cs-441524 and remdesivir are renally excreted
if ou see themincrease water consumption

Adverse effects of molnupiravir

GI - decreased appetite, nausea, hypersalivation and vomiting
folded ears and broken whiskers
hematologic and hepatic - increased ALT an neutropenia

Why don’t we use molupiravir as first line drug for FIP

higher rates of side effects, antiviral stewardship, viral evolution risks, teratogenicity

FIP - supportive care

pain managemnt, fluid therapy and critical care, nurisng and stress, caregiver support, nutrition and BCS, antiemetics, Ocular/neuro meds

FIP patient monitoring

first few days - improvent should be rapid, effusion can worsen for 1-2 days especially post IV tx, neurological sigsn can also intially appera
weight daily and blood work monthly (HTC, albumin, globulins and bilirubin)

FIP relapse

uncommon espcially after 3 months tx
often with different clincial form
escalate therpay from last time

Prioin lession

neurodegeneration vacuoles
dissemiantion through nerves (vagus and obex) and lymphoid

Scrapies - excretion

placental tissues/fluids