An Ancient Immunity

By Sarah Richardson
Jan 1, 1997 6:00 AMNov 12, 2019 5:53 AM


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This past year will be remembered as a watershed year for AIDS research. Among the breakthroughs was the finding, in August, that a mutation in the ckr-5 gene, which encodes the receptor that the virus uses as a doorway into a cell, provided resistance to hiv infection. Then, in September, the surprising extent of that resistance was documented by population geneticist Stephen O’Brien and his colleagues at the National Cancer Institute, who studied 1,955 people at high risk for contracting the virus.

Roughly 1 percent of the study group carried two copies of the mutated ckr-5 gene, says O’Brien--and they had all resisted infection despite multiple exposures to hiv. A much larger percentage--about 14 percent--carried one mutated ckr-5 gene. Although these people could and did become infected with hiv, the progression from asymptomatic infection to aids was likely to take two to three years longer in them than in a person with two normal copies of ckr-5.

The differences in vulnerability have to do with the number of available doorways into an immune cell, O’Brien explains. People with one mutated ckr-5 gene have half as many doorways for hiv as people with two normal genes, so the virus spreads more slowly in them. People with mutations in both copies of the gene are completely lacking in the doorways that hiv prefers, so the virus can’t infect enough cells to establish itself in the body.

Surprisingly, Caucasians were nearly ten times as likely to carry the beneficial mutation as African Americans. Roughly 20 percent of the Caucasians in the study group carried one copy of the gene--making it more common, O’Brien notes, than red hair. O’Brien suspects that it cropped up in the Caucasian lineage after the common ancestor of Africans and Caucasians migrated out of Africa around 150,000 to 200,000 years ago. But a random mutation, he adds, wouldn’t have risen to such a high frequency in the population unless it had also provided some benefit long before the current aids epidemic. That benefit, O’Brien suspects, may have been protection against some ancient scourge. An aids epidemic before historic times might have wiped out large numbers of Caucasians, he says. Or the cause might have been some other rather highly pathogenic microbe that also used the ckr-5 receptor as an entry point.

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