Rediff.com« Back to articlePrint this article

Indian-origin expert may have found a way to attack HIV

August 05, 2008 08:54 IST

Sudhir Paul of the University of Texas-Houston Medical School and his team may have found a way to attack the weakest link in HIV.

According to a paper in the journal Autoimmune Reviews, the team has found an unchanging part of the virus that can be attacked using abzymes -- that is, antibodies that have enzymatic activity.

Paul, director of the Chemical Immunology Research Center at the university, says HIV needs a complex solution because it mutates so fast that antibodies against the coat proteins on a given viral unit do not work on new viral units that emerge rapidly.

Which was why Paul and his team went about hunting for a part of the HIV that does not change. They found it in gp120 (glycoprotein 120), one of the proteins that form the package of the virus.

As in all proteins, gp120 is made up of a chain of smaller units, the amino acids. But Paul's team found that the 421st to 433rd amino acids in gp120 appear unable to change, which also makes them the ideal target for a drug.

"We call it the Achilles heel," says Paul of the short chain of vulnerable amino acids that attach themselves to a protein receptor called CD4, found on the T cells (white blood cells that get infected with HIV).

These cells are usually doughty defenders of the body, but, after HIV infects them, the eventual results are a weakened immune system that leaves the body open to other infections.

Other white blood cells called B cells are responsible for making protective antibodies against infectious viruses, but they have difficulty making antibodies for the crucial Achilles heel area.

Normal proteins stimulate the B cells to make the protective antibodies. But when the Achilles heel portion of gp120 binds to antibodies on the cells, it stimulates them to death -- the cellular equivalent of hara-kiri.

Ironically, uninfected humans do make small amounts of protective antibodies, but the antibody production decreases after HIV infection. This is why the Achilles heel portion is called a superantigen.

"The reason we have difficulty combating HIV is because of this superantigenic region," Paul says. The result is that there being few B white blood cells to target the vulnerable unit, while there are many being fooled into targeting the constantly changing parts of gp120, thus wasting their resources.

Paul says there is evidence that there was an ancestral form of HIV long before monkeys transmitted modern HIV to humans a few decades ago.

As evidence, Paul cites the similarity of the crucial section of gp120 with a section of ancient viral DNA that long ago found its way into the human genome.

He also suggests that the ability of healthy humans and animals without infection to make weakly protective antibodies suggests that the ancestral HIV-like segment came in early in evolution, perhaps as early as the appearance of the first immune system -- that was in sharks.

Finding a vulnerable part of HIV is essential for making a vaccine. But Paul and his team have advanced one step: they decided to use an antibody with enzymatic properties, called a catalytic antibody, to attack the unchanging part of gp120.

"A catalytic antibody can break down thousands of target antigens. Usually, an antibody can manage a maximum of two," says Paul. Better, he says, the catalytic antibodies destroy the target antigen permanently, in a way standard antibodies cannot.

Paul earned his PhD in biochemistry at The All India Institute of Medical Sciences in 1981. He did post-doctoral work, also in biochemistry at the University of Kiel. He worked at the University of Oklahoma and the University of Nebraska before joining the University of Texas in 1998.

And in 1989, his team discovered catalytic antibodies to proteins.

Now he and his current team are trying to find ways to deal with HIV worldwide.

"If India and Africa are going to solve the HIV problem, it is going be through a vaccine, he says. "We are hot on the trail of that vaccine."

A correspondent in New York