A New Way to Resist HIV Infection?

SEATTLE--Researchers may have found a new explanation for why some people seem to fend off the AIDS virus. According to a study reported here on Saturday at the annual meeting of the American Association for the Advancement of Science (which publishes ScienceNOW), immune cells from a handful of people--including two men infected with HIV who later cleared the virus--blocked HIV after it entered the cells, suggesting that these people carry an unknown cellular actor that protects them. Some AIDS experts call the findings provocative but too preliminary to conclude whether they explain some cases of resistance.

In a series of test tube experiments, a team led by Miles Cloyd of the University of Texas Medical Branch in Galveston found that of 50 healthy people they tested who had no known HIV exposure, up to 15% appeared to have CD4 lymphocytes--the white blood cells selectively destroyed by HIV--that resist infection with certain strains of the virus. Now, looking to explain those results, Cloyd's group has found in cell culture that while the RNA that codes for the virus enters resistant cells and makes a DNA copy of itself, the cells somehow fail to crank out more virus. Cloyd says the manufacturing process may get hung up when HIV tries to insert its DNA into the host's DNA, or else when the cell attempts to make viral RNA from the inserted DNA.

Cloyd also described a separate study of CD4 cells from two cases of "transient infection"--men exposed to HIV through their partners who became infected but appeared virus-free by sensitive tests several months later, even though they weren't taking anti-HIV drugs. Like cells from some healthy people, the men's cells seemed to block HIV from replicating once it entered the cells.

Scientists already knew of two kinds of resistance--one in which people inherit the ability to mount a strong immune response to HIV, and another that occurs in people born with a defect in the receptor on the surfaces of cells that HIV uses to gain entry. But "there's a large segment of this population that we don't have any clue why they're resistant," says Cloyd, and the new findings "may play a role in that."

Other AIDS researchers at the session, however, say it is difficult to evaluate Cloyd's new work without seeing published results and more clinical data. "It's highly believable that there will be host factors that will block HIV postentry," says Richard Koup of the Aaron Diamond AIDS Research Center in New York City. "But it's too early to say how important this will be in HIV transmission."

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