Viral Diseases - Syke's Flashcards
What antiviral drugs are used to treat feline herpesviral infections?
famciclovir, idoxuridine, cidofovir
T/F: Antiviral drugs can act synergistically with immunomodulators.
TRUE
Why do antiviral drugs have greater toxicity than antibiotics? Examples of toxicity?
can also affect the function of host cell machinery; bone marrow suppression, immunosuppression, carcinogenic, teratogenic
What is a nucleoside analogue?
resembles host nucleosides, which are nitrogenous bases with an attached sugar molecule used as a building block for the formation of DNA or RNA
T/F: Latent viral infections cannot be treated with nucleoside analogues.
True - replication of virus is necessary for the drugs to work; however, reactivation of these infections can be reduced in frequency or prevented
What is the mechanism of action of famciclovir?
prodrug that is activated by the herpesviral enzyme thymidine kinase, which phosphorylates them to a monophosphate form. Host cell enzymes then phosphorylate the drugs further to triphosphate forms, which concentrate in virus-infected cells and interfere with viral DNA replication via inhibition of the viral DNA polymerase enzyme
T/F: Feline herpesvirus-1 infections are more susceptible to acyclovir than human herpes simplex.
FALSE
What is the mechanism of action of acyclovir/valacyclovir?
guanosine analogue; interferes with viral DNA polymerase and DNA synthesis. Activity requires viral thymidine kinase (TK)
What is the mechanism of action of lysine?
lysine is an amino acid that interferes with herpesviral replication by a poorly understood mechanism (antagonism of arginine may be involved)
What are interferons?
cytokines with antiviral properties
What are type I interferons? What cells produce them?
IFN-alpha, IFN-beta, IFN-omega; leukocytes and fibroblasts product in response to viral infection
What is the mechanism of action of type I interferons in disease mitigation?
activate natural killer cells, increase expression of MHC class I molecules, and have antitumor activity
______ is the only type II interferon and is produced by T lymphocytes and NK cells in response to antigenic stimulation.
IFN-gamma – plays a critical role in clearance of intracellular pathogens by macrophages
Why can recominant human IFN-alpha lose efficacy after parenteral administration?
due to development of neutralizing antibodies (loses activity after 3 or 7 weeks)
T/F: Recombinant human IFN-alpha is not effective when given orally because it is degraded by gastric acid.
False - although it is degraded by gastric acid, studies have shown beneficial outcomes for FHV-1, FeLV and FIV infections (presumably because immunomodulation follows mucosal absorption of the drug)
What is the mechanism of action of IFN-omega?
type I interferon – secreted by virus-infected leukocytes, increases macrophage and NK cell activity, has antiviral activity against FeLV, FHV-1, feline calicivirus, paroviruses, and feline coronavirus; also has antitumor activity
Side effects of treatment with recombinant feline IFN-omega?
lethargy, fever, vomiting, diarrhea, anorexia (esp at higher doses); some bloodwork abnormalities
How do glucocorticoids aid in treatment of viral diseases?
dampen an overzealous immune response that contributes to the pathology of infection
FIV is what type of virus? What animals does it infect?
enveloped, RNA virus - Lentivirus genus of Retroviridae; infects domestic and wild cats + hyenas
Structure of retroviruses such as FIV?
three-layered structure - inner genome-nucleocapsid complex with helical symmetry, icosahedral capsid, and an envelope with glycoprotein spikes
Major genes of the FIV genome?
gag (encodes virion core proteins – capsid, nucleocapsid, and matrix); pol (encodes reverse transcriptase, protease and integrase enzymes); env (encodes surface and transmembrane virion envelope glycoproteins)
FIV invades cells via what receptors?
CD134 (primary) - expressed on feline CD4+ T cells, B cells, and activated macrophages; CXCR4 (secondary) - chemokine receptor
T/F: Latency is one mechanism by which retroviruses can evade the host immune system.
TRUE
T/F: Retroviruses can survive outside of the host for long periods of time.
False - survive only minutes outside the host and are susceptible to disinfection
What is the major mode of transmission of FIV?
bites - FIV is shed in high concentrations in saliva
What is the main cellular target for FIV?
CD4+ T cell; can also infect CD8+ T cells, B cells, macrophages, dendritic cells, microglia, and astrocytes
T/F: Cats with FIV often have a latent infection for years or for life.
False - it is NOT a latent infection, it is a SUBCLINICAL infection because the virus production CONTINUES at low levels
What are the three phases of FIV infection?
acute (primary), subclinical, and terminal
What neoplasias are most commonly reported with FIV?
Lymphoma - especially B cell lymphoma*; FIV-infected cats are 5X more likely to develop lymphoma than non-infected cats (and more likely to develop it earlier)
What screening test is used for testing for FIV infection?
ELISA assay that detects antibody against FIV
What is the most common abnormality on a chemistry profile for a cat infected with FIV?
hyperproteinemia – results from increased gamma-globulin concentration and is a direct result of FIV infection
T/F: A positive FIV ELISA equals FIV infection in a cat over 6 months of age.
True - because the virus establishes a lifelong, persistent infection; false positive results occur rarely due to operator error or nonspecific reactivity against tissue culture components after vaccination
Why might a kitten under 6 months of age have a false positive FIV screening test?
maternal antiboides (infection or vaccination of the queen)
Why might a cat have a false negative FIV ELISA?
can occur early in the course of illness because cats may take up to 60 days to develop an antibody response
What drug should be avoided when treating dermatophytosis in an FIV-positive cat? Why?
griseofulvin – associated with bone marrow suppression in FIV-positive cats
What type of virus is FeLV?
enveloped, RNA virus - genus Gamaretrovirus, family retroviridae
What species can be infected with FeLV?
domestic cats; wild felids - including Iberian Lynx
T/F: FeLV infection progresses more rapidly than FIV infection and is more pathogenic, so more infected cats die of FeLV-related disease.
TRUE
Mode of transmission of FeLV?
close contact with salivary secretions (licking, mutual grooming, shared food/water dishes); lesser extent - biting, transplacental, milk, blood transfusion
T/F: FeLV can survive for long periods of time outside of the host.
False - all retroviruses survive poorly outside of the host and are readily inactivated by disinfectants, soap, and dessication
Is the median age of cats infected with FeLV younger or older than cats with FIV?
Younger - median age of cats infected with FeLV is 3 years
T/F: After exposure to the FeLV virus, all cats will become infected.
False - some cats can develop an abortive infection whereby the virus is eliminated
What are the most common neoplasias associated with FeLV?
Lymphoma - especiallly T cell lymphoma** - can by thymic, multicentric, spinal, renal, or ocular lymphoma
Multiple fibrosarcomas in young cats are a result of infection with what virus?
FeLV infection that recombines with ceullar oncogenes to form feline sarcoma virus**
Cutaneous horns are associated with what virus?
FeLV infection - due to benign keratinocyte hyperplasia
What screening test is used for testing for FeLV infection?
free FeLV Antigen** in serum (detects soluble p27 capsid protein)
T/F: Kittens can be tested at any time for FeLV because maternal antibodies do not interfere with the FeLV testing.
True - because the ELISA test for ANTIGEN
T/F: FeLV vaccination produces sterilizing immunity.
False - cats can still develop infection but vaccination prevents PROGRESSIVE infection
T/F: There is no effective treatment for FeLV infections.
True - manage secondary complications; equivocal benefit described in some studies for interferon-omega and interferon-alpha or the antiviral drug zidovudine
A positive IFA for FeLV indicates the virus has spread where?
bone marrow – almost always results in progressive infection; IFA tests for FeLV antigen in blood cells
When might a PCR test for FeLV be useful?
screen for blood donors (in conjunction with antigen testing); test for regressive infection when FeLV is strongly suspected but antigen tests are negative
What is the main capside protein in the FeLV virion?
p27
What are the main structures in the envelope of the FeLV virion?
gp70 glycoprotein, transmembrane protein p15E
How does the viral envelope protein p15E of the FeLV virus contribute to immunosuppression?
inhibits T and B cell function, inhibits cytotoxic lymphocyte responses, alters monocyte morphology and distribution, impaired cytokine production and responsiveness
Does FeLV impair T or B cells more?
T cells (lesser extent also impairs B cell function)
What does PCR for FeLV detect?
FeLV RNA (RT-PCR), or proviral DNA
What type of virus is FHV-1?
large, enveloped DNA virus
Latent infections with FHV-1 primarily occur in what tissue(s)?
trigeminal ganglia
T/F: FHV-1 survives for long periods of time outside of the host.
False - survives a maximum of 18 hours at room temperature, readily inactivated by drying and most disinfectants
Primary mode of transmission of FHV-1?
close contact, lesser extent fomite spread or aerosol transmission
Reactivation of shedding of FHV-1 can occur _____ days after stress, and can last for ____.
4-12 days after stress; shedding for 1-13 days (mean 7 days)
The presence of corneal ulceration raises suspicion for which viral infection?
FHV-1
T/F: Apparently healthy cats can shed FHV-1.
True - thus, PCR results for FHV-1 must be interpreted with caution
T/F: ELISA testing for FHV-1 can aid in diagnosis of infection.
False - due to high prevalence of subclinical exposure to the virus
Histopathological findings with facial dermatitis due to FHV-1
epidermal ulceration and necrosis that can extend to superficial dermis, infiltration with neutrophils, eosinophils, histiocytes, plasma cells, lymphocytes; intranuclear viral inculsions can be identified
T/F: No respiratory viral vaccine prevents infection, carrier state, or reactivation of viral shedding with FHV-1.
True - can reduce disease severity, duration of shedding, viral infectivity, and load of latent virus in the trigeminal ganglia
What type of virus are papillomaviruses?
non-enveloped, icosahedral viruses with a circular double-stranded DNA genome
T/F: Papillomaviruses can survive in the environment for prolonged periods of time.
True - resistant in the environment and can survive detergents and high temperatures
Papillomaviruses are classified based on what part of the genome?
L1 capsid protein gene sequence
Papillomaviruses have been associated with what diseases in cats?
feline viral plaques, Bowenoid in situ carcinomas, invasive cutaneous SCC, feline sarcoids
Papillomaviruses have been associated with what diseases in dogs?
oral papillomatosis, cutaneous exophytic papillomas (warts), cutaneous endophytic papillomas (inverted warts), pigmented cutaneous plaques, cutaneous in situ SCC, invasive cutaneous SCC, oral SCC
Initial infection and viral amplification with Papillomaviruses occur in what cells?
within keratinocytes in the stratum basale
What viral proteins stimulate cell cycle proliferation and lead to enhanced proliferation of cells in the stratum spinosum and stratum granulosum when infected with papillomavirus?
early viral proteins (E proteins)
Where are the late viral products (virus capsid proteins L1 and L2) first expressed with papillomavirus infections?
stratum spinosum
What clinical manifestation of papillomavirus is due to a latent infection?
feline sarcoids
Some papillomaviruses produce proteins that degrade what important tumor suppressors?
p53 and retinoblastoma protein
T/F: Mature virions are shed with cells that exfoliate from the stratum corneum with papillomavirus infections.
TRUE
Methods for detection of papillomavirus
PCR assay, IHC, in situ hybridization, electron microscopy
For what clinical manifestation of papillomavirus infection would IHC not be useful?
feline sarcoids (latent infection)
What is koilocytosis?
papillomavirus-induced cytopathic effects = extensive cytoplasmic vacuolation and nuclear pyknosis
Histopathological findings with feline sarcoids
dermal fibroblastic proliferations with overlying epithelial hyperplasia that includes long, thin rete ridges that extend into the tumor (may be confused with sarcomas!)
