Indian American pinpoints Achilles heel of killer HIV

July 16th, 2008 - 1:59 pm ICT by IANS  

Washington, July 16 (IANS) University of Texas researchers led by Indian American Sudhir Paul have pinpointed the Achilles heel in the protective mechanism of HIV, the virus that claims millions of lives worldwide when it develops into AIDS. The finding may give hope to millions of HIV positive people. The weak spot is hidden in the HIV envelope protein gp120. This protein is essential for HIV attachment to host cells, which initiate infection and eventually lead to AIDS.

The Achilles heel, a tiny stretch of amino acids numbered 421-433 on gp120, is now under study as a target for therapeutic intervention.

Paul, who led the research and co-authored the paper said: “Unlike the changeable regions of its envelope, HIV needs at least one region that must remain constant to attach to cells.”

If this region changes, HIV cannot infect cells, he said, adding: “Equally important, HIV does not want this constant region to provoke the body’s defence system.”

So, HIV uses the same constant cellular attachment site to silence B lymphocytes - the antibody producing cells. The result is that the body is fooled into making abundant antibodies to the changeable regions of HIV but not to its cellular attachment site.

“Immunologists call such regions super-antigens. HIV’s cleverness is unmatched. No other virus uses this trick to evade the body’s defences,” said Paul, an alumni of the All India Institute of Medical Sciences in New Delhi.

For the same reason, no HIV preventive vaccine that stimulates production of protective antibodies is available.

First reported in the early 1980s, HIV has spread across developing countries, infecting some 33 million people by 2007 according to a WHO report.

Paul’s group has engineered antibodies with enzymatic activity, also known as abzymes, which can attack the Achilles heel of the virus in a precise way.

“The abzymes recognise essentially all of the diverse HIV forms found across the world. This solves the problem of HIV changeability. The next step is to confirm our theory in human clinical trials,” Paul said.

A single abzyme molecule deactivates thousands of virus particles, permanently, unlike regular antibodies that act only against a single virus particle, and their anti-viral HIV effect is weaker.

“The work of Paul’s group is highly innovative. They have identified antibodies that, instead of passively binding to the target molecule, are able to fragment it and destroy its function,” said Steven J. Norris of the University of Texas Medical School.

“Their recent work indicates that naturally occurring catalytic antibodies, particularly those of the IgA subtype, may be useful in the treatment and prevention of HIV infection,” he said.

The abzymes are derived from HIV negative people with the autoimmune disease lupus and a small number of HIV positive people who do not require treatment and do not get AIDS.

These findings have appeared in the latest issue of the journal Autoimmunity Reviews.

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