Basics of Human Immunodeficiency Virus (HIV)

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Transcript Basics of Human Immunodeficiency Virus (HIV)

Basics of
Human Immunodeficiency Virus
(HIV)
Brian Rybarczyk, PhD
University of North CarolinaChapel Hill
Nature of HIV Infection

HIV is a retrovirus having RNA as its genome
(humans have a DNA genome)

HIV infects immune cells ultimately destroying a
person’s defense against foreign invaders

Uses CD4 receptor on immune cells to infect
(enter) cells
How Does HIV cause AIDS?

Ultimately, HIV destroys a person’s
immune cells to a level that the body
cannot protect from foreign invaders

This opens up the host for a multitude of
other diseases including Pneumocystis
carinii, Tuberculosis, Kaposi sarcoma
Three Important HIV Enzymes

Reverse Transcriptase (RT) – converts HIV RNA
genome into a DNA copy

Integrase (IN) – inserts the HIV DNA copy into
host genome

Protease (PR) – cuts and processes immature
HIV proteins into mature, functioning proteins
HIV lifecycle
1. HIV binds to
immune cells
using CD4 and a
coreceptor
2. HIV fuses with
cell membrane
3. RT
and injects core copies HIV
with RNA
RNA into
genome
DNA
4. Integrase
incorporates
HIV genome
copy into host
genome
CD4
coreceptor
5. Protease processes
immature proteins into
mature HIV proteins
6. Virus buds from
cell producing many
viral progeny
Strategies of HIV Therapy
Reverse transcriptase blockers
nucleoside analogs: AZT, 3TC, d4T
non-nucleoside: nevirapine
CD4
coreceptor
Entry Inhibitors
T-20
Protease Blockers
indinavir, ritonavir
Development of Drug Resistant
HIV Mutants
Anti-HIV drug
HIV
variants
susceptible
to drug
HIV
variant
resistant
to drug
How do mutations arise in HIV?

HIV’s reverse transcriptase does not copy the HIV RNA
genome into DNA accurately

This leads to mutations that can be beneficial or harmful
to HIV

Mutations that allow viruses to survive will produce
progeny that will also be resistant

Anti-HIV drugs provide a selective pressure that allows
HIV to develop drug resistant mutants
Why is there no cure for HIV?

High mutation rate caused by RT

The outer protein envelope (gp120) mutates,
therefore the host’s immune system cannot
recognize and destroy all HIV present

HIV permanently incorporates into host DNA

Development of drug resistant mutants