RETROVIRUSES

What is a retrovirus?

• group of viruses that contain TWO single-stranded linear RNA molecules

• carries genetic blueprint in the form of RNA

• reverse transcriptase makes DNA from RNA (RNA dependent DNA polymerase)

How does a retrovirus infect a cell such as in HIV?

• receptor binding proteins invade host cell via interaction with these proteins and specific receptors on host cell

• HIV infects CD4+ T cells with receptor binding proteins gp120 and gp41

Why are retroviruses so genetically variable?

reverse transcription is error prone and replicate fast, sequence changes constantly

what is the purpose of reverse transcriptase?

used to make viral DNA from viral RNA

What are the treatment courses of HIV?

A combination of 2 NRTIs and 1 other drug such as an NNRTI, PI, Int. I or entry inhibitor. three drugs total.

What is the mechanism of action of reverse transcriptase inhibitors?

• NRTI (nucleoside reverse transcriptase inhibitors)

  • target: reverse transcriptase

  • enter cell and be triphosphorylated to be active

  • competitively inhibit incorporation of normal nucelotides > lack of 3’ OH group

  • ex. zidovudine

• NNRTI (non-nucleoside reverse transcriptase inhibitors)

  • target: reverse transcriptase

  • bind to a hydrophobic pocket in p66 subunit of RT

  • non-competitive inhbitor

  • DO NOT require phosphorylation for activity

What is the mechanism of action of protease inhibitors?

• prevent T-cells that have been infected with HIV from producing new copies of virus

• lock up and disable protease

• no cleavage; can’t cup up DNA to leave, pieces of virus are stuck inside

• problem: resistance, side effects, complaince

What is the mechanism of action of integrase inhibitors?

• integrase (permanent incorporation step); blocks catalytic activity

What is the mechanism of action of entry inhibitors?

• block entry into host host

What do integrase inhibitors end with?

“gravir”