Molecular Biology of HIV

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Molecular Biology of HIV

• www.hopkins-aids.edu/hiv_lifecycle/
• www.who.int/hiv/en
• hivinsite.ucsf.edu/InSite.jsp?dockb-02-01-02

HIV budding from an infected cell.
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A Brief History of AIDS
1981 CDC reports unusual incidences of pneumonia
caused by Pneumocystis carinii and of skin
cancers, Kaposi's sarcoma. Patient's immune
system were impaired. 1982 CDC recognized a new
disease Acquired Immune Deficiency Syndrome
(AIDS). 1983 The infectious agent was isolated
by L. Montagnier (Paris) and R. C. Gallo (NIH).
First called it HTLV for human T-cell leukemia
virus. Now called Human Immunodeficiency Virus,
or HIV. 2001 500,000 - 1,000,000 people infected
in the US. More than 30 million people infected
world-wide 70 in Sub-Saharan Africa.
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Fulfilling Koch's postulates difficult, because
of the long latency period.
Dewhurst S., Ramothea L.W. da Cruz 1 Whetter L.
Frontiers in Bioscience, 5, d30-49, January 1,
2000
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Some of the evidence that HIV causes
AIDS 1. Virus can be isolated from almost all
with the disease. 2. Advanced disease correlates
with higher virus titer. 3. Asymptomatic
individuals that have antibodies to coat
proteins later develop the disease. 4.
Recipients of contaminated blood frequently
develop AIDS. 5. About 30 of children born to
infected mothers are infected with the virus
those that are, go on to develop AIDS, but
uninfected siblings do not. 6. AIDS does not
appear in a new locality without the prior
presence of HIV. 7. Treatments that target the
virus alleviate the disease.
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Structure of HIV Sarcophagus-shaped capsid
contains 2 copies of RNA genome (SS () strand),
reverse transcriptase, an integrase, a RNase, and
a protease. P7 coats the RNA, and P24 forms the
nucleocapsid structure, which is enclosed by a
lipid bilayer. Lipid bilayer comes from the
host cell, and contains two viral-encoded
proteins, gp41 and gp120. gp120 binds the CD4
receptor on helper T cells.
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How does HIV kill cells? The virus
replicates by budding through the cell membrane.
This does not necessarily kill the cells. Cells
die by autofusion, syncytial formation and
apoptosis. Other mechanisms may await discovery.
1. Autofusion CD4 and gp120/41 proteins mediate
fusion and intracellular vesicle formation.
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2. Syncytium formation gp120/41 proteins on
infected cells bind to CD4 receptors on normal
cells, causing cell fusion.
Infected cell
Normal cell
3. Apoptosis An infected helper T cell can direct
an uninfected T helper to undergo apoptosis
(programmed cell death). Apoptosis can be normal,
for example, to eliminate auto-reactive T
lymphocytes to establish self-tolerance.
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• HIV is a retrovirus.
• A more specific name is Lentivirus.
• Retroviruses have a RNA genome that is replicated
  via a DNA intermediate in an infected host cell.
  DNA also integrates in the host genome to form
  provirus.
• HIV is more complex than the RNA tumor viruses,
  such as MLV, murine leukemia virus.
• HIV encodes a number of extra regulatory and
  accessory proteins.

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