Biology of HIV1 Retrovirus

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Biology of HIV-1 Retrovirus

• Matthew Engel
• BME 501
• October 17, 2006

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Global Epidemic
Youth under age 25 account for over half of all
new HIV infections each year (worldwide) . Young
women are the majority (62) of this population.
Many sexually active young people at risk for
HIV do not perceive themselves to be at risk,
even in those countries with very high
prevalence. Moreover, most young people living
with HIV do not know they are infected (1).
In the US, women are the fastest growing
population becoming infected with HIV. African
American and Hispanic women are the most rapidly
expanding subset developing AIDS. Combined these
categories represent 25 of US women, 80 females
infected.
(2)
(1) The Henry J, Kaiser Family Foundation.
HIV/AIDS Policy Fact Sheet. The Global Impact of
HIV/AIDS on Youth. July 2004. (2) V. Simon, D.
D. Ho, and Q. Abdool Karim, Lancet 368 (9534),
489 (2006).
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General Structure of HIV Provirus
Taken from (1)
gag precursor protein. Codes for matrix protein
(MA NLS/NES), capsid (CA) and nucleocapsid
protein (NC) assemblies. CA forms conical core
containing genomic RNA and NC ribonucleoprotein
complex (2). pro HIV protease. Cleaves gag,
pro, pol, and sometimes env. pol encodes
reverse transcriptase holoenzyme and
integrase. env surface and transmembrane
glycoproteins.
Long terminal repeats
Long terminal repeats Transcriptional control
Encapsidation sequence
Primary transcript
(1) John Coffin, S. H., Harold Varmus (1997)
Retroviruses, Cold Spring Harbor Laboratory
Press. (2) Ternois, F., Sticht, J., Duquerroy,
S., Krausslich, H. G., and Rey, F. A. (2005) The
HIV-1 capsid protein C-terminal domain in complex
with a virus assembly inhibitor, Nature
structural molecular biology 12, 678-682.
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HIV-1 Genomic Organization
HIV genome 9200 nt. Alternate start codons. Gag
termination codon bypassed by frame shifting.
Multiple transcripts
Codes for envelope proteins.
John Coffin, S. H., Harold Varmus (1997)
Retroviruses, Cold Spring Harbor Laboratory
Press.
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Lifecycle Sites of Intervention
Envelope glycoproteins Gp120 and Gp41 Lipid
bilayer (env) surrounding capsid
Primary receptor CD4
Direct translation from viral RNA
Host lymphocyte translation
Proteolytic cleavage
R. Wolkowicz and G. P. Nolan, Gene therapy 12
(6), 467 (2005).
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Gp120
CD4 receptor
V3 Domain
e- density. 1s
gp120
50x50x20 Å
base
tip
Fab antibody
Kwong, P. D., et al. (1998), Nature 393, 48-659.
Huang, C. C et al. (2005) Science 310, 1025-1028.
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V3 Epitope
gp120
17b and X5 antibodies bind to coreceptor
attachment site. The other monoclonal antibodies
are linked solely to the V3 domain. Suggests
high degree of accessibility for generating an
immune response.
Immunoglobulins
Huang, C. C et al. (2005) Science 310,
1025-1028.