Transcript Clinical Group - Chulabhorn Research Institute

The gp41 fragment (purple) consists
of a cytoplasmic tail and a
hydrophobic membrane-spanning
domain and is joined with the
larger gp120 component (blue line)
via fusion domain.The gp120
glycoprotein has several
glycosylation sites and hypervariable
loops (eg. V3), which lead to antigenic
variation between viral strains.
The CD4-binding region (red) is located
toward the center of the complex and consists of components from both the gp120
and gp41 fragment Envelope glycoprotein complex of
HIV-1
How it might be stopped (Drug development
RNA is convert into double strand DNA by RT
- Drugs called RT inhibitors can interrupt this
process.ART inhibitor drugs, such as AZT and
3TC, can disrupt the early stage of viral
reproduction
Enz integrase incorporates the virus’ genetic
material into the T cell’s DNA
-Drug called integrase inhibitors, which are
designed to halt this process, are in development
Disrupting the assembly line
Protease Enz cut viral proteins into shorter
pieces so that they can incorporated into
new viruses
-Protease inhibitors block this stage of
reproduction by neutralizing the enzyme.
They’re even more effective when
combined with RT inhibitors
The high mutation yield of HIV
-We know that resistance emerges
because of the appearance of many
viral variants
-The generation of diversity could be
because ?
1. Replication is “ error prone” which is
what most people say
2. Because the virus makes so many
copies of itself each day (which does not
mean that it is really more error prone
than other retroviruses) or a
combination of points (1) and (2)
If the virus is really error prone read paper by
L. A. Loeb and J. M. Essigmann et.al. 1999.
Proc. Natl. Acad. Sci. USA “ Lethal mutagenesis
of HIV with mutagenic nucleoside analogs”
This paper test the hypothesis that a further
increase in the mutation rate by promutagenic
nucleoside analog would abolish viral replication
The HIV virus binds
to the cell surface of a
CD4+ lymphocyte. The
binding attachment
occurs through an
interaction of the
viral glycoprotein
gp120/gp41
and the CD4 receptor
complex on the cell surface
HIV binding via CD4 receptor
The End
Thank you