Indian- Origin Scientist makes HIV research breakthrough

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Indian-origin scientist claims to uncovering Achilles Heel of HIV

Washington, July 16 (ANI): An Indian-origin researcher studying Human

Immunodeficiency Virus (HIV) at The University of Texas Medical School at

Houston claims that his team has uncovered the Achilles heel in the armour of

the HIV virus.

Sudhir , Ph.D., has found that this 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 Acquired Immunodeficiency Syndrome or

AIDS.

Normally the bodys immune defences can ward off viruses by making proteins

called antibodies that bind the virus, but no HIV preventative vaccine that

stimulates production of protective antibodies is available.

The Achilles heel, a tiny stretch of amino acids numbered 421-433 on gp120, is

now under study as a target for therapeutic intervention.

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. Equally important, HIV does not want this constant region to

provoke the bodys defense 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 superantigens. HIVs

cleverness is unmatched. No other virus uses this trick to evade the bodys

defenses, said .

is the senior author on a paper about this theory in a June issue of the

journal Autoimmunity Reviews. Additional data supporting the theory are to be

presented at the XVII International AIDS Conference Aug. 3-8 in Mexico City in

two studies titled Survivors of HIV infection produce potent, broadly

neutralizing IgAs directed to the superantigenic region of the gp120 CD4 binding

site and Prospective clinical utility and evolutionary implication of broadly

neutralizing antibody fragments to HIV gp120 superantigenic epitope.

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 recognize 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,” said.

He stressed that abzymes degrade the virus permanently unlike regular

antibodies. A single abzyme molecule inactivates thousands of virus particles.

Regular antibodies inactivate only one virus particle, and their anti-viral HIV

effect is weaker.

Usually, 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.

We discovered that disturbed immunological events in lupus patients can generate

abzymes to the Achilles heel of HIV. The human genome has accumulated over

millions of years of evolution a lot of viral fragments called endogenous

retroviral sequences. These endogenous retroviral sequences are overproduced in

people with lupus, and an immune response to such a sequence that resembles the

Achilles heel can explain the production of abzymes in lupus.

A small minority of HIV positive people also start producing the abzymes after

decades of the infection. The immune system in some people can cope with HIV

after all, said Planque, lead author and UT Medical School at Houston

graduate student. Carl Hanson, Ph.D., who heads the Retrovirus Diagnostic

Section of the Viral and Rickettsial Disease Laboratory of the California

Department of Public Health, has shown that the abzymes neutralize infection of

human blood cells by diverse strains of HIV from various parts of the world.

Human blood cells are the only cells that HIV infects.

This is an entirely new finding. It is a novel antibody that appears to be very

effective in killing the HIV virus. The main question now is if this can be

applied to developing vaccine and possibly used as a microbicide to prevent

sexual transmission, said C. Montefiori, Ph.D., director of the Laboratory

for AIDS Vaccine Research & Development at Duke University Medical Center.

The abzymes are now under development for HIV immunotherapy by infusion into

blood. They could also be used to guard against sexual HIV transmission as

topical vaginal or rectal formulations.

The journal article is titled Catalytic antibodies to HIV: Physiological role

and potential clinical utility and is published in the latest issue of the

journal Autoimmunity Reviews. (ANI)

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