Body's own antibodies may drive new strains of HIV.

2003 APR 9 - (NewsRx.com & NewsRx.net) -- Scientists in California have provided the first detailed look at how human antibodies, proteins critical for the body's defense against invading pathogens, may actually drive human immunodeficiency virus (HIV) to mutate and escape detection by the immune system.

The findings, reported online March 18, 2003, in the Proceedings of the National Academy of Sciences USA, may be key in efforts to develop an effective AIDS vaccine.

A team led by Douglas D. Richman, MD, a virologist and physician with the Veterans Affairs (VA) San Diego Healthcare System and the University of California, San Diego (UCSD) School of Medicine, found that patients infected with HIV rapidly develop a strong antibody response against the virus. But the same antibodies tasked with recognizing and disabling the germ appear to force its ongoing evolution into new strains that dance around the antibody response and continue to replicate.

"The neutralizing antibodies are exerting a very strong selective pressure on the virus, and the virus is continually mutating to avoid it," said Richman, a noted AIDS researcher who recently won VA's Middleton Award, the agency's highest honor for biomedical researchers.

The researchers used sophisticated new technology, made by California-based ViroLogic, Inc., to clone actual virus from the blood plasma of HIV patients and genetically combine it with a gene that makes luciferase, the same light-emitting enzyme in fireflies. The glowing enzyme helped the scientists track the virus' replication.

Richman and colleagues took viral samples periodically from HIV patients and incubated the virus with antibody-containing plasma samples from the same patients. Blood plasma contains antibodies but no white blood cells. This way, the researchers could tease out the effects of antibodies alone on the virus, independent of the rest of the immune system.

The results, based on tests of 19 patients over 39 months, showed that most patients developed a high concentration, or titer, of antibodies to HIV within a few months, and the antibodies continually changed their "spectrum of activity" to keep pace with the ever-changing virus. That is, the antibodies evolved in their ability to recognize different protein shapes on the outer coating of the virus.