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Defensins Inhibit
HIV
Researchers at
Rockefeller University in the Aaron
Diamond AIDS Research Center (ADARC) in
New York have identified proteins that
inhibit the human immunodeficiency virus
using mass spectrometry.
Scientists may have finally identified an
elusive protein that allows some people to
remain healthy for many years after being
infected by the virus that causes AIDS.
The discovery could lead to a new approach
to fighting the deadly disease.
AIDS researchers have been intrigued for
sometime as to why 1-5% of patients
infected by HIV can live for 10 or 15
years, or even longer, with no apparent
damage to their immune systems. Dr. Robert
Lehrer, a professor of medicine at UCLA,
who led the discovery of human defensins
in the 1980s first noticed that certain
immune cells (CD8 T-cells) in these
patients seemed to produce some protective
factor. Since then scientists have been
working to identify the factor(s).
In the mid-1990s, a group of compounds
known as beta-chemokines were discovered
that suppressed some, but not all, types
of the virus. The New York scientists, led
by Dr. Linqi Zhang, think the defensins
account for most of the rest of the
protective factor.
Using the selective isolation of these
proteins on a chip, the researchers used
mass spectrometry to measure the molecular
weights of the proteins and their
fragments to search a database of known
proteins.
Three proteins, alpha-defensins 1, 2, and
3, appear to work in combination to
prevent the virus' replication, or
copying, in the body. Defensins were first
described by scientists Ganz and Lehrer in
1985 and were thought to be made
exclusively by neutrophils, a specialized
immune system cell, to kill bacteria. The
Rockefeller/ADARC researchers have found
that they are also made by CD8+ T-cells
and inhibit the replication of HIV by an
as-yet-undetermined mechanism.
One application already being worked on is
a test if infected people have CD8 T-cells
make defensins before putting the proteins
to work in a treatment.
The authors note that using defensins as a
medicine might be difficult, in part
because they are difficult to manufacture
outside the cell. "This is not going to be
the ultimate solution, but it's another
weapon we can use in our arsenal against
HIV," said Dr. David Ho, the Director of
the Aaron Diamond AIDS Research Center in
New York.
The full report appears in the September
26 issue of Science
Express.
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