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