What kind of virus is HIV?
Lentivirus
Describe Lentiviruses
Retroviruses that can infect NON-dividing cells. HIV 1 and HIV 2 are human lentiviruses.
- HIV 1 is more pathogenic than HIV 2.
- 4 HIV groups (M, O, N, P)
What is the predominant form of HIV in the US?
HIV 1 M subtype B
What three enzymes must be brought by the HIV into the host cell?
- reverse transcriptase
- integrase
- protease
What are the 6 steps of the viral replication cycle?
- Attachment
- Entry/Fusion
- Uncoating
- DNA and protein synthesis
- Assembly
- Release
What are the subunits of glycoprotein on HIV envelope associated with attachment and entry/fusion?
gp120 & gp41
Describe HIV Attachment & Entry/Fusion Process
- gp120 subunit binds to CD4 receptor on helper T cell. This induces a conformation change to expose co-receptor binding site of gp120.
- CCR5 on helper T cell binds to the co-receptor binding site of gp120. This induces a second conformational change in the gp41 subunit.
- N-terminal fusion peptide gets inserted into the host cell’s membrane.
What are the co-receptors on T cells and what viruses uses them?
- CCR5: used by M Tropic R5 Virus
- CXCR4: used by T Tropic X4 Virus
- Both CCR5 & CXCR4: Dual/Mixed (D/M) Tropic Virus
*CCR5 is used by most virus strains, but viruses can evolve to use CXCR4 later time in infeciton.
True or False: In addition to CD4, a coreceptor is needed for HIV to enter the host cell.
True
What 3 processes are carried out by reverse transcriptase?
- Reverse transcription of ssRNA –> viral ssDNA
* RNA-dependent DNA polymerase - RNase H degrades ssRNA
* RNase H - Production of viral dsDNA
* DNA-dependent DNA polymerase
** all three enzymatic activities are on the HIV RT enzyme.
HIV replication is a highly error-prone process due to
frequent mutations during reverse transcription
What is the function of an integrase?
It helps identify integration site on host DNA and executes the viral strand transfer (irreversible) in the host DNA.
What are the most commonly used agents against HIV?
reverse transcriptase inhibitors (NRTIs)
*competitive inhibitor of RT
What is the protein of HIV associated with the capsid?
p24
What is the protein of HIV associated with the matrix?
p17
What are the three major classes of structural genes of HIV?
- env (gp120, gp41)
- gag (p24, p17)
- pol (reverse transcriptase, integrase, protease)
What NRTIs do we have to know?
- Zidovudine
- Abacavir
- Lamivudine
- Emtricitabine
- TDF & TAF
What NRTI is the first ARV drug developed?
Zidovudine
- thymidine analog
What NRTI has the potential risk for the severe hypersensitivity and cardiac disease?
Abacavir
What NRTI is also effective for Hep B?
Lamivudine & Emtricitabine
What NRTI is commonly used in combination pills?
TDF & TAF
What antiretroviral agents are protease inhibitors (PI)?
- Lopinavir
- Rotnavir
*-navir
What antiretroviral agent is an integrase inhibitor?
Raltegra
What antiretroviral agent is a co-receptor (CCR5) inhibitor?
Maraviroc
