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Mutant gene may be key to AIDS cure

BOSTON (AP) — A surprising number of people — perhaps one in 100 whites — have genes that can enable them to escape AIDS infection despite having risky sex thousands of times, scientists discovered.
The finding answers one mystery of the AIDS epidemic — how some people get away with breaking all the safe sex rules — and opens new possibilities for treating and preventing the disease.
If scientists can find a way to mimic the effects of this inborn genetic shield, it may be possible to create a pill that will keep people from becoming infected with the AIDS virus.
The key is a mutation in the genes that direct the body’s defenses against disease. In this case, one of the genes is missing a chunk of information, so the body fails to produce a particular protein. This protein is one of the docking points the AIDS virus needs to invade cells.
Those who are born with two copies of the mutant gene — one from Mom, one from Dad — appear to be highly resistant to AIDS infection, although experts are not sure if their protection is absolute.
“What’s very surprising is how common this mutation is. We originally thought people with this would be one in a million. Actually, it’s more like one in 100” white people, said Dr. Nathan R. Landau of the Aaron Diamond AIDS Research Center in New York City.
In addition, a surprising 20 percent or so of whites were found to have one copy. The effects of having one copy are still unclear. But the researchers believe it makes people somewhat less likely to get infected and may help them survive much longer once infection occurs.
Experts believe there soon will be a simple blood test to reveal whether people have one, two or no copies of the gene.
Already, some experts worry that people will throw away their condoms if they learn they have two copies.
“That would be folly. We are just on the threshold of understanding all of this,” said Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases.
Landau and colleagues studied two gay men who had watched 40 or 50 of their friends and lovers die of AIDS. They volunteered because they wondered why their own high exposure to the virus had not led to infection too.
In a report in Friday’s issue of the journal “Cell,” the scientists reported the answer: Both men have two mutant copies of a newly discovered gene called CCR5.
“All over the world, wherever people look, there is a small fraction of people who seem not to get infected” despite multiple exposure, said Dr. Robert W. Doms of the University of Pennsylvania Medical Center. “For whites, it is often going to be because of this mutation. But this may just be the beginning of an interesting story.”
In another report scheduled for publication in the Aug. 22 issue of the journal “Nature,” he and colleagues describe looking for the mutant gene in people of European, African and Asian heritage; only whites had it.
But Doms and others suspect that people of other ethnic origins will turn out to have other protective genes.
Landau’s and Doms’ groups were among five to report the discovery of CCR5, also known as CKR-5, in June. Ordinarily, CCR5 acts as a hitching post on blood cells for chemokines, chemical messages that summon help to the site of inflammation.
However, when HIV gets into the body, they found it latches onto CCR5 as well as CD4, another protein that has long been recognized as an AIDS docking point.
The latest work shows that without CCR5, infection with the most common sexually transmitted varieties of HIV is unlikely, although experts caution that some forms of the virus may still be able to get in by attaching to other spots on blood cells.
AIDS researchers have long wondered why some people who got infected at the epidemic’s start in the early 1980s are still alive and seemingly healthy, while others die quickly.
Having one mutant CCR5 gene may provide at least part of the answer. The Diamond researchers found that infected cells with one copy of the gene produce four to 10 times less HIV than usual.
Landau said drug companies are already working on drugs to block CCR5 as a way of keeping HIV out of cells.

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