Basics of Human Immunodeficiency Virus (HIV)

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Transcript Basics of Human Immunodeficiency Virus (HIV)

Basics of
Human Immunodeficiency Virus
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
2. HIV fuses with
cell membrane
3. RT
and injects core copies HIV
with RNA
RNA into
4. Integrase
HIV genome
copy into host
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
Entry Inhibitors
Protease Blockers
indinavir, ritonavir
Development of Drug Resistant
HIV Mutants
Anti-HIV drug
to drug
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