Understanding HIV:
CCR5 and fusin—co-receptors for HIV
January 2003 View PDF En
español
Chemokines
Coinciding with the discovery of these novel receptors was the
discovery that naturally occurring immune chemicals, called beta-chemokines,
bind up CCR5 and CXCR4 and help block HIV from infecting cells.
This is depicted graphically below. For many years it has been supposed
that CD8+ cells produce a factor capable of suppressing HIV infection
of CD4+ cells.
Beta-Chemokines block entry of HIV into
cells
In 2001, Dr. Robert Gallo’s group identified such a factor,
which appears to be a combination of chemicals (called chemokines):
MIP-1-alpha, MIP-1-beta and Rantes. The fact that CCR5 not only
allows HIV entry into CD4 bearing cells, but is also a receptor
for these chemokines explains two important aspects of the interaction
between the immune system and the virus. When the CD8+ cells effectively
make a large quantity of the chemokines, they may fill up and block
the “doorway” for infection provided by the CCR5 protein.
Conversely, when levels of the chemokines are low or absent for
any reason, the virus is free to more easily infect cells because
the CCR5 receptor protein is readily available to it.
Collectively, the back-to-back discoveries of the role of the chemokines
and the CCR5 receptor site shed important new light on how HIV infects
cells and may explain why the disease process differs from person
to person. It should also be noted that another CD8+-derived antiviral
factor (CAF), documented first by Dr. Jay Levy (co-discoverer of
HIV), has been shown to inhibit HIV replication, but the origin
of this factor remains unidentified.
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