Small Animal Retroviridae (Exam 2) Flashcards

1
Q

What is special about retroviruses?

A

Retro = backwards
Reverse transcriptase: RNA dependent polymerase, creates complementary DNA, inserts backwards into host genome, no proof-reading
Used to detect RNA in PCR

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2
Q

How are retroviruses classified?

A

Nucleotide sequence
Core appearance based on transmission electron microscopy
Antigenic gag similarity
Pathophysiology: acute (rapidly) transforming, chronic (slowly) transforming), immunosuppressive

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3
Q

What is the general structure of retroviruses?

A

Enveloped with glycoprotein spikes (bi-lipid membrane from host cell)
Icosahedral capsid (contains, core proteins, RNA)
Diploid
Positive sense single stranded RNA

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4
Q

What genes do all retroviruses contain?

A

gag: group-specific antigen, capsid
pol: polymerase, integrase, reverse transcriptase
env: envelope, transmembrane surface proteins
+/- oncogenes

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5
Q

What is important about the envelope of retroviruses?

A

High mutation rate = antigenic variation
Envelope spike determines cell tropism and species specificity
Virus is unstable in environment, direct contact or cell transfer required

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6
Q

Describe general retrovirus replication

A

Virion contains 2 copies of the positive sense single stranded RNA genome
Reverse transcription of the viral RNA genome by reverse transcriptase produces dsDNA
dsDNA is transported to the nucleus where it integrates into host cell’s DNA (provirus)
Transcription is carried out by host to make viral mRNAs and vRNA genomes

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7
Q

Describe the steps of retrovirus replication

A
  1. cell binding- env to host
  2. fusion - core in cytoplasm
  3. reverse txn: RNA –> dsDNA +LTR
  4. nuclear entry
  5. integration via integrase (provirus in host genome)
  6. DNA transcription by host –> mRNA
  7. translation in cytoplasm, (a) proteins, (b) ssRNA
  8. env mRNA translocated
  9. env translation
  10. transmembrane proteins (env) assembled in golgi apparatus
  11. virion assembly
  12. budding
  13. release - infectious virions
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8
Q

What are the implications associated with permanent DNA integration in host cell?

A

Once host genome infected, host replicates viral genome (virus doesn’t have to replicate)

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9
Q

What is endogenization in regards to retroviruses?

A

Provirus integration into germline
Source of rapid mutations in host (evolution, tumorigenesis, immune development, autoimmune disease)
Source of virus recombination (may interact with exogenous virus)

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10
Q

What are the 2 types of retrovirus infections?

A

Transforming, oncogenic
Immunodeficiency, immune-mediated

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11
Q

What are the 2 types of retroviral oncogenesis?

A

Slowly transforming
Rapidly transforming

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12
Q

What are characteristics of slowly transforming oncogenesis?

A

Promoter inserted near/acting on host c-onc
Provirus randomly inserted into host genome

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13
Q

What are characteristics of rapidly transforming oncogenesis?

A

Contains v-onc
Need to be replication competent or get help from another virus

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14
Q

Define: c-onc

A

Cellular
Normal gene belonging to host, under biologic controls
Can be promoted by virus LTR

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15
Q

Define: v-onc

A

Viral
Mutated, upregulated/dysregulated by virus, no longer under normal controls

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16
Q

What are the important feline retroviruses?

A

Feline leukemia virus (FeLV)
Feline immunodeficiency virus (FIV)

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17
Q

What is the only horizontally infectious strain of FeLV?

A

A

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18
Q

What are the 2 disease routes of FeLV?

A

Immunodeficiency
Neoplasia

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19
Q

What are the most important strains of FeLV?

A

A, B

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20
Q

What is the clinical presentation of FeLV?

A

Fever
Anorexia, weight loss
Non-healing wounds
Secondary infections (skin, GI, respiratory)

21
Q

What is the signalment of those infected with FeLV?

A

Younger
Avg 3 years

22
Q

What syndromes are associated with FeLV?

A

Neoplasia
Anemia
Immunodeficiency (fading kitten syndrome)
Pathology depends on subtype

23
Q

How is FeLV shed?

A

Saliva, blood, urine, feces, milk

24
Q

Where does FeLV replicate?

A

Receptors are universal
Lymphocytes, monocytes, salivary epithelium

25
Q

How is FeLV transmitted?

A

Horizontal: close contact, grooming, fighting
Vertical: maternal transfer

26
Q

What groups are at highest risk for FeLV?

A

Outdoor tom cats

27
Q

What are the outcomes of FeLV exposure?

A

Abortive: robust immune response, clears infection
Regressive: partial immune response, suppressed replication (provirus in cells, recrudescence possible)
Progressive: immune response ineffective, unchecked viral replication, poor prognosis

28
Q

What is the life cycle of FeLV?

A
29
Q

How does FeLV neoplasia occur?

A

Lmphoma/symphosarcoma: insertional (+) or c-onc

30
Q

What myeloproliferative diseases are associated with FeLV neoplasia?

A

Erythemic myelosis
Granulocytic leukemia
Erythroleukemia
Myelofibrosis

31
Q

What coinfection is common with FeLV?

A

Feline sarcoma virus (fibrosarcoma)

32
Q

Symptoms of immune-mediated FeLV?

A

Immune complexes - hypersensitivity type 3
Glomerulonephritis

33
Q

Symptoms of antibody dependent cytotoxicity of FeLV?

A

Feline oncovirus membrane associated antigen bodies
Lymphocyte depletion

34
Q

What are secondary infections of FeLV?

A

FIP, toxoplasmosis, aspergillus sp., mycoplasma hemofelis

35
Q

How is FeLV prevented/controlled?

A

Test and cull or segregate
Lower risk factors (spay/neuter, keep indoors)
Vaccination (core kitten series) = killed or canarypox vectored vaccine

36
Q

How is FeLV diagnosed?

A

Screening: SNAP test (antigen)
Confirmatory: ELISA, IFA, PCR (provirus, endogenous), virus isolation

37
Q

How is FIV transmitted?

A

Horizontal: shed in saliva, blood
Vertical: transplacental (rare)

38
Q

What symptoms are associated with FIV?

A

Acute: fever, lymphadenopathy
Late stage: feline acquired immunodeficiency disease

39
Q

What is the incubation period of FIV?

A

Long, asymptomatic incubation period
Average = 7yrs

40
Q

What are the subtypes of FIV?

A

A, B widespread

41
Q

What is the pathogenesis of FIV?

A

Tropism for CD4+/CD8+ T cells
Lymphopenia in acute phase
Rebound in latent stage (inversion CD8+ –> CD4+)
Gradual T cell decline –> immunodeficiency

42
Q

What is special about FIV anitbodies?

A

NOT neutralizing (no vaccine not effective)

43
Q

Is cell mediated or humoral (antibody) immunity more impacted with FIV?

A

Cell-mediated immunity
Antibody responses pretty much normal

44
Q

What are the clinical signs of FIV?

A

Older cat w unexplained illness
Recurrent fever
Weight loss, wasting, unkempt coat
Lymphadenopathy
Leukopenia, anemia
Chronic infections: gingivostomatitis, dermatitis, diarrhea, cystitis, pneumonia

45
Q

What is the life cycle of FIV?

A
46
Q

What diagnostics are used for FIV?

A

Screening: SNAP test (antibody)
Confirmatory test: PCR, western blot

47
Q

What is the prognosis of cats diagnosed with FIV?

A

Lifespan can be equal to uninfected cats with management
Early detection of opportunistic disease or cancer important
Moderate risk to infecting co-housed cats

48
Q

When would you expect false negatives on a FIV/FeLV SNAP test?

A

FeLV: if in regression phase
FIV: if too soon to detect Ab/Ag

49
Q

When would you expect false positives on a FIV/FeLV SNAP test?

A

FIV: if vx given
Maternal Abs in kitten