Protective AIDS Mutation: A Double-Edged Sword?

A genetic mutation that can delay the onset of AIDS in people infected with HIV may hasten death after symptoms of the disease appear. A report in tomorrow's Lancet suggests that, once HIV infection progresses to AIDS, patients with a mutated copy of the gene for what's called the CCR5 receptor die 6 months sooner, on average, than those with good copies. Researchers are surprised by the finding, which must be corroborated by larger studies.

For the HIV virus to get into a cell and replicate, it must latch onto certain proteins that stud the surface of immune cells. Last year, researchers identified one of these footholds, a receptor called CCR5. They also discovered that a few people, who lack this receptor because both copies of the gene coding for it were bad, seemed to resist infection with HIV. Another study (Science, 27 September 1996, p. 1856) revealed that people with a single mutated copy of the receptor gene tended to live without symptoms of AIDS for years longer than those with both copies intact.

But a mutation may actually be a mixed blessing, argues Peter Garred of the Tissue-Typing Laboratory at the Rigshospitalet in Copenhagen, Denmark. For 11 years he and his colleagues have been tracking the health of 99 gay men infected with HIV. So far, they have examined the DNA of 56 who have died, looking for mutations in the CCR5 gene. The 45 men who carried normal copies lived up to 6.5 years past their diagnosis with AIDS, although the average survival was 17 months. Those with a mutation in one copy of the gene faced much bleaker prospects: The longest any of these 11 men survived after diagnosis was 20 months and the average was just 11 months.

The findings are "provocative," says Michael Dean of the National Cancer Institute. Dean points out that after the emergence of virulent strains that circumvent CCR5—one of the steps that heralds the arrival of AIDS symptoms—mutations on the gene for that receptor should have no effect on life expectancy. Garred speculates, however, that the faulty receptor could somehow be hampering the immune system, perhaps making patients more vulnerable to virulent HIV strains.

Posted in Health, Biology