Lecture 12 - Retroviruses

What do retroviruses require for replication?

Double stranded DNA provirus

What are the consequences of provirus integration into host genome? What percent of the human genome consists of retroviruses?

-Virus divides when cell divides

-Integration into germ cells results in vertical transmission

-10%

What are the classes of retrovirus drugs?

-Nucleoside analog reverse transcriptase inhibitors (chain terminators)

-Non-nucleoside analog reverse transcriptase inhibitors

-Integrase inhibitors

-Protease inhibitors

How is a retrovirus gene organized?

Long terminal repeat - gag (group associated antigens) - pol (polymerase) - env (envelope proteins) - long terminal repeat

What are the three modes of transformation of retroviruses?

1. Rapid - virus carries oncogene (weeks)

2. Intermediate - virus lacks oncogene and is transformed by cis-activation (months)

3. Slow - virus lacks an oncogene and is activated by trans-activation

What does retrovirus reverse transcriptase lack? Why is this important?

-3’-5’ exonuclease activity

-Causes more nucleotide errors (quasispecies)

What type of retrovirus is avian leukosis virus (ALV)? What is an important characteristic?

-Alpharetrovirus

-At least 10 different virus subgroups with different disease patterns and outcomes

What type of retrovirus is RSV? What is an important characteristic?

-Alpharetrovirus

-Carries a virus-oncogene that allows for rapid transformation of cells

What type of retrovirus is bovine leukemia virus? What is an important characteristic? How is it controlled?

-Deltaretrovirus

-Infected cattle are asymptomatic for live making quarantines difficult

-Test and remove positive animals

What are examples of gammaretroviruses? What type of disease outcomes are they responsible for? How is it transmitted?

-Ex. FeLV and FeSV

-Neoplastic, anemia, chronic inflammation, immunodeficiency

-Horizontal (blood, saliva) and vertical transmission

What type of retrovirus is HIV? What are important characteristics?

-Lentivirus

-Persistent/chronic, slowly progressing disease with a long incubation period

What type of retrovirus is equine infectious anemia (EIA)? What are important characteristics? How is it controlled?

-Lentivirus

-Quasispecies - envelope gene mutations lead to new virus variants over course of infection (viral genome you start with is NOT the same as the one you end with)

-Control vectors, serological testing, isolate infected horses, restrict movement

What type of retrovirus is visna? What does it cause? How is it transmitted?

-Lentivirus

-Causes demyelinating leukoencephalomyelitis (weakness, weight-loss, paresis/paralysis)

-Through mucosal secretions or vertical transmission

What type of retrovirus is feline immunodeficiency virus (FIV)? What are some important characteristics? How is it transmitted?

-Lentivirus

-Immunodeficiency disease associated with progressive immunosuppression and opportunistic infections

-Horizontal (oral) transmission

What are the four stages in the disease progression of FIV? What occurs in each?

1. Acute phase - lymphadenopathy, fever, leukopenia

2. Subclinical phase - absence of clinical disease

3. Chronic phase - decreased CD8:CD4 ratio, increased viral load, chronic and progressive anemia

4. Terminal stage - progressive immune dysfunction with opportunistic infections and occasionally neoplasia