Scientists ID Genetic Cause of HIV Virulence
Loss of one function of one gene makes the difference, study says
THURSDAY, June 15, 2006 (HealthDay News) -- Researchers say they've identified the genetic mutation that makes the AIDS virus so deadly.
The loss of one function of one gene in HIV-1 is responsible for the virus' virulence, according to a report by an international team of researchers who compared the human virus with its close relatives, a family of viruses called simian immunodeficiency virus (SIV), which infects primates.
The faulty gene, designated Nef, has many functions, said Dr. Frank Kirchoff, professor of virology at the University of Ulm in Germany, and lead author of the report. One function is to lower the immune system's response to infection, reducing the production of protective T cells. A mutation has removed that function from HIV-1, which means the immune system of someone infected with the virus literally works itself to death, overproducing T cells, Kirchoff said.
"The body is not able to maintain the immune response for years," he explained. "T cells are lost every day. At some point, the capacity of the immune system is exhausted, and the infection becomes AIDS."
The study findings appear in the June 16 issue of the journal Cell.
Studies have shown that the Nef gene retains its full capabilities in most of the HIV-like viruses that infect monkeys, so those viruses aren't as deadly as HIV, the researchers said. Monkeys infected with those viruses get a chronic disease that is not necessarily fatal.
The discovery of the Nef gene flaw could influence AIDS treatment, Kirchoff said. "A few years back, it was thought that boosting the immune response would be a good thing," he said. "This shows that we do not want the highest levels of immune response. We want to have some immune response, but not the highest levels of chronic immune activation."
Another possible new treatment approach would be to develop a vaccine using an HIV strain engineered to contain a fully functioning Nef gene, according to an accompanying commentary in the journal by infectious-disease experts at the University of Texas Southwestern Medical Center.
"It is genetically possible to do that, given the techniques we have today, but whether it would provide the desired results would be questionable," said J. Victor Garcia, professor of internal medicine at the medical center's division of infectious diseases and co-author of the commentary.
The report itself is "certainly very unorthodox," Garcia said. "But these provocative results should be followed up."
There's one major problem that makes the development of such a vaccine difficult, perhaps impossible, added Dr. Beatrice H. Hahn, professor of medicine and microbiology at the University of Alabama at Birmingham, a member of the research team and one of the leading experts on HIV. She was the researcher who determined that the HIV-1 sprang from an SIV mutation that infects chimpanzees.
"It would be interesting to know what such an HIV strain would do," Hahn said. "But there is no good animal model for HIV."
The lack of such a model means the vaccine with the altered HIV molecule would have to be tested in humans, Hahn said. "Even if you restore Nef function, I would not recommend inoculating people with it," she said.
Hahn is trying a different approach, working to see if modifications of monkey viruses could be an effective vaccine. "We are taking a virus that is found in rhesus macaques and we try to electively knock out the down-regulation function," she said. "Assuming that we can do that, we would give it to macaques to test its action."
For more on HIV and AIDS, visit the U.S. National Institutes of Health.