Viral Diseases - Syke's Flashcards

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1
Q

What antiviral drugs are used to treat feline herpesviral infections?

A

famciclovir, idoxuridine, cidofovir

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2
Q

T/F: Antiviral drugs can act synergistically with immunomodulators.

A

TRUE

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3
Q

Why do antiviral drugs have greater toxicity than antibiotics? Examples of toxicity?

A

can also affect the function of host cell machinery; bone marrow suppression, immunosuppression, carcinogenic, teratogenic

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4
Q

What is a nucleoside analogue?

A

resembles host nucleosides, which are nitrogenous bases with an attached sugar molecule used as a building block for the formation of DNA or RNA

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5
Q

T/F: Latent viral infections cannot be treated with nucleoside analogues.

A

True - replication of virus is necessary for the drugs to work; however, reactivation of these infections can be reduced in frequency or prevented

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6
Q

What is the mechanism of action of famciclovir?

A

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

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7
Q

T/F: Feline herpesvirus-1 infections are more susceptible to acyclovir than human herpes simplex.

A

FALSE

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8
Q

What is the mechanism of action of acyclovir/valacyclovir?

A

guanosine analogue; interferes with viral DNA polymerase and DNA synthesis. Activity requires viral thymidine kinase (TK)

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9
Q

What is the mechanism of action of lysine?

A

lysine is an amino acid that interferes with herpesviral replication by a poorly understood mechanism (antagonism of arginine may be involved)

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10
Q

What are interferons?

A

cytokines with antiviral properties

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11
Q

What are type I interferons? What cells produce them?

A

IFN-alpha, IFN-beta, IFN-omega; leukocytes and fibroblasts product in response to viral infection

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12
Q

What is the mechanism of action of type I interferons in disease mitigation?

A

activate natural killer cells, increase expression of MHC class I molecules, and have antitumor activity

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13
Q

______ is the only type II interferon and is produced by T lymphocytes and NK cells in response to antigenic stimulation.

A

IFN-gamma – plays a critical role in clearance of intracellular pathogens by macrophages

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14
Q

Why can recominant human IFN-alpha lose efficacy after parenteral administration?

A

due to development of neutralizing antibodies (loses activity after 3 or 7 weeks)

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15
Q

T/F: Recombinant human IFN-alpha is not effective when given orally because it is degraded by gastric acid.

A

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)

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16
Q

What is the mechanism of action of IFN-omega?

A

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

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17
Q

Side effects of treatment with recombinant feline IFN-omega?

A

lethargy, fever, vomiting, diarrhea, anorexia (esp at higher doses); some bloodwork abnormalities

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18
Q

How do glucocorticoids aid in treatment of viral diseases?

A

dampen an overzealous immune response that contributes to the pathology of infection

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19
Q

FIV is what type of virus? What animals does it infect?

A

enveloped, RNA virus - Lentivirus genus of Retroviridae; infects domestic and wild cats + hyenas

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20
Q

Structure of retroviruses such as FIV?

A

three-layered structure - inner genome-nucleocapsid complex with helical symmetry, icosahedral capsid, and an envelope with glycoprotein spikes

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21
Q

Major genes of the FIV genome?

A

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)

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22
Q

FIV invades cells via what receptors?

A

CD134 (primary) - expressed on feline CD4+ T cells, B cells, and activated macrophages; CXCR4 (secondary) - chemokine receptor

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23
Q

T/F: Latency is one mechanism by which retroviruses can evade the host immune system.

A

TRUE

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24
Q

T/F: Retroviruses can survive outside of the host for long periods of time.

A

False - survive only minutes outside the host and are susceptible to disinfection

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25
Q

What is the major mode of transmission of FIV?

A

bites - FIV is shed in high concentrations in saliva

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26
Q

What is the main cellular target for FIV?

A

CD4+ T cell; can also infect CD8+ T cells, B cells, macrophages, dendritic cells, microglia, and astrocytes

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27
Q

T/F: Cats with FIV often have a latent infection for years or for life.

A

False - it is NOT a latent infection, it is a SUBCLINICAL infection because the virus production CONTINUES at low levels

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28
Q

What are the three phases of FIV infection?

A

acute (primary), subclinical, and terminal

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29
Q

What neoplasias are most commonly reported with FIV?

A

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)

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30
Q

What screening test is used for testing for FIV infection?

A

ELISA assay that detects antibody against FIV

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31
Q

What is the most common abnormality on a chemistry profile for a cat infected with FIV?

A

hyperproteinemia – results from increased gamma-globulin concentration and is a direct result of FIV infection

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32
Q

T/F: A positive FIV ELISA equals FIV infection in a cat over 6 months of age.

A

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

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33
Q

Why might a kitten under 6 months of age have a false positive FIV screening test?

A

maternal antiboides (infection or vaccination of the queen)

34
Q

Why might a cat have a false negative FIV ELISA?

A

can occur early in the course of illness because cats may take up to 60 days to develop an antibody response

35
Q

What drug should be avoided when treating dermatophytosis in an FIV-positive cat? Why?

A

griseofulvin – associated with bone marrow suppression in FIV-positive cats

36
Q

What type of virus is FeLV?

A

enveloped, RNA virus - genus Gamaretrovirus, family retroviridae

37
Q

What species can be infected with FeLV?

A

domestic cats; wild felids - including Iberian Lynx

38
Q

T/F: FeLV infection progresses more rapidly than FIV infection and is more pathogenic, so more infected cats die of FeLV-related disease.

A

TRUE

39
Q

Mode of transmission of FeLV?

A

close contact with salivary secretions (licking, mutual grooming, shared food/water dishes); lesser extent - biting, transplacental, milk, blood transfusion

40
Q

T/F: FeLV can survive for long periods of time outside of the host.

A

False - all retroviruses survive poorly outside of the host and are readily inactivated by disinfectants, soap, and dessication

41
Q

Is the median age of cats infected with FeLV younger or older than cats with FIV?

A

Younger - median age of cats infected with FeLV is 3 years

42
Q

T/F: After exposure to the FeLV virus, all cats will become infected.

A

False - some cats can develop an abortive infection whereby the virus is eliminated

43
Q

What are the most common neoplasias associated with FeLV?

A

Lymphoma - especiallly T cell lymphoma** - can by thymic, multicentric, spinal, renal, or ocular lymphoma

44
Q

Multiple fibrosarcomas in young cats are a result of infection with what virus?

A

FeLV infection that recombines with ceullar oncogenes to form feline sarcoma virus**

45
Q

Cutaneous horns are associated with what virus?

A

FeLV infection - due to benign keratinocyte hyperplasia

46
Q

What screening test is used for testing for FeLV infection?

A

free FeLV Antigen** in serum (detects soluble p27 capsid protein)

47
Q

T/F: Kittens can be tested at any time for FeLV because maternal antibodies do not interfere with the FeLV testing.

A

True - because the ELISA test for ANTIGEN

48
Q

T/F: FeLV vaccination produces sterilizing immunity.

A

False - cats can still develop infection but vaccination prevents PROGRESSIVE infection

49
Q

T/F: There is no effective treatment for FeLV infections.

A

True - manage secondary complications; equivocal benefit described in some studies for interferon-omega and interferon-alpha or the antiviral drug zidovudine

50
Q

A positive IFA for FeLV indicates the virus has spread where?

A

bone marrow – almost always results in progressive infection; IFA tests for FeLV antigen in blood cells

51
Q

When might a PCR test for FeLV be useful?

A

screen for blood donors (in conjunction with antigen testing); test for regressive infection when FeLV is strongly suspected but antigen tests are negative

52
Q

What is the main capside protein in the FeLV virion?

A

p27

53
Q

What are the main structures in the envelope of the FeLV virion?

A

gp70 glycoprotein, transmembrane protein p15E

54
Q

How does the viral envelope protein p15E of the FeLV virus contribute to immunosuppression?

A

inhibits T and B cell function, inhibits cytotoxic lymphocyte responses, alters monocyte morphology and distribution, impaired cytokine production and responsiveness

55
Q

Does FeLV impair T or B cells more?

A

T cells (lesser extent also impairs B cell function)

56
Q

What does PCR for FeLV detect?

A

FeLV RNA (RT-PCR), or proviral DNA

57
Q

What type of virus is FHV-1?

A

large, enveloped DNA virus

58
Q

Latent infections with FHV-1 primarily occur in what tissue(s)?

A

trigeminal ganglia

59
Q

T/F: FHV-1 survives for long periods of time outside of the host.

A

False - survives a maximum of 18 hours at room temperature, readily inactivated by drying and most disinfectants

60
Q

Primary mode of transmission of FHV-1?

A

close contact, lesser extent fomite spread or aerosol transmission

61
Q

Reactivation of shedding of FHV-1 can occur _____ days after stress, and can last for ____.

A

4-12 days after stress; shedding for 1-13 days (mean 7 days)

62
Q

The presence of corneal ulceration raises suspicion for which viral infection?

A

FHV-1

63
Q

T/F: Apparently healthy cats can shed FHV-1.

A

True - thus, PCR results for FHV-1 must be interpreted with caution

64
Q

T/F: ELISA testing for FHV-1 can aid in diagnosis of infection.

A

False - due to high prevalence of subclinical exposure to the virus

65
Q

Histopathological findings with facial dermatitis due to FHV-1

A

epidermal ulceration and necrosis that can extend to superficial dermis, infiltration with neutrophils, eosinophils, histiocytes, plasma cells, lymphocytes; intranuclear viral inculsions can be identified

66
Q

T/F: No respiratory viral vaccine prevents infection, carrier state, or reactivation of viral shedding with FHV-1.

A

True - can reduce disease severity, duration of shedding, viral infectivity, and load of latent virus in the trigeminal ganglia

67
Q

What type of virus are papillomaviruses?

A

non-enveloped, icosahedral viruses with a circular double-stranded DNA genome

68
Q

T/F: Papillomaviruses can survive in the environment for prolonged periods of time.

A

True - resistant in the environment and can survive detergents and high temperatures

69
Q

Papillomaviruses are classified based on what part of the genome?

A

L1 capsid protein gene sequence

70
Q

Papillomaviruses have been associated with what diseases in cats?

A

feline viral plaques, Bowenoid in situ carcinomas, invasive cutaneous SCC, feline sarcoids

71
Q

Papillomaviruses have been associated with what diseases in dogs?

A

oral papillomatosis, cutaneous exophytic papillomas (warts), cutaneous endophytic papillomas (inverted warts), pigmented cutaneous plaques, cutaneous in situ SCC, invasive cutaneous SCC, oral SCC

72
Q

Initial infection and viral amplification with Papillomaviruses occur in what cells?

A

within keratinocytes in the stratum basale

73
Q

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?

A

early viral proteins (E proteins)

74
Q

Where are the late viral products (virus capsid proteins L1 and L2) first expressed with papillomavirus infections?

A

stratum spinosum

75
Q

What clinical manifestation of papillomavirus is due to a latent infection?

A

feline sarcoids

76
Q

Some papillomaviruses produce proteins that degrade what important tumor suppressors?

A

p53 and retinoblastoma protein

77
Q

T/F: Mature virions are shed with cells that exfoliate from the stratum corneum with papillomavirus infections.

A

TRUE

78
Q

Methods for detection of papillomavirus

A

PCR assay, IHC, in situ hybridization, electron microscopy

79
Q

For what clinical manifestation of papillomavirus infection would IHC not be useful?

A

feline sarcoids (latent infection)

80
Q

What is koilocytosis?

A

papillomavirus-induced cytopathic effects = extensive cytoplasmic vacuolation and nuclear pyknosis

81
Q

Histopathological findings with feline sarcoids

A

dermal fibroblastic proliferations with overlying epithelial hyperplasia that includes long, thin rete ridges that extend into the tumor (may be confused with sarcomas!)