Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.
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San Francisco Examiner - December 3, 1998
Ulysses Torassa, Examiner Medical Writer
Their study, to published in Friday's edition of in the journal Science, is the latest in a recent string of discoveries of genetic variations in patients with HIV that help explain, at least in part, why some people rapidly come down with AIDS while others can carry the virus for more than 20 years and not develop the disease.
Several drug companies are reportedly looking into developing therapies for HIV based on the insights gained from figuring out why some people are able to resist the infection and others aren't.
The latest discovery focuses on a gene's so-called "promoter region," which supplies the code to manufacture a receptor that sits on the outside of certain immune cells. The receptor acts as a gateway for a newly acquired virus to enter those cells, where it sets up shop, copying itself as many as a billion times a day.
Later, the virus breaks out and begins killing immune cells, leading to the destruction of the immune system and thus to AIDS.
The promoter region of the gene helps control how often and when it is turned on and begins manufacturing the protein for the receptor. The gene is called CCR5.
"What we think is that it makes a little bit more CCR5," said Stephen J. O'Brien, of the National Cancer Institute, one of the authors of the new study. "It simply says, "Hey, Mr. Virus, take over. Here's more doorways to get in.' "
Using genetic profiles of more than 2,600 infected people, O'Brien and his colleagues found that 10 to 17 percent of those who came down with AIDS within 3-1/4 years after infection had a variation in that region of the gene. The average time between infection and AIDS is about 10 years, based on data collected before anti-retroviral drugs were in widespread use, according to Susan P. Buchbinder, of the San Francisco Department of Public Health, another of the study's authors.
The researchers found the genetic variation appeared in 12.7 percent of Caucasians studied and in 6.7 percent of African Americans.
Earlier work by O'Brien and his colleagues found that another genetic variation in the CCR5 gene had an opposite effect - it conferred a great deal of resistence to HIV, probably because it leads the body to make less of the receptor, called a chemokine receptor.
Other recent work by O'Brien and others on a separate gene that also codes for a chemokine receptor has been linked to retarded HIV infection. And chemokines, which are immune-system molecules, have been shown to block HIV infection, presumably because they sit in the receptor sites that the virus needs as gateways to infect cells.
"As we tease out the genetic variables that determine whether someone progresses rapidly or whether someone is resistant to progression, the answer keeps coming back to chemokine or chemokine receptors," said Warner Greene, a UC-San Francisco professor and director of the Gladstone Institute of Immunology and Virology. "It's clearly telling us that chemokine receptors are an excellent drug target. If we could block them, we'd be in good shape."
Still, even the study's authors don't believe genes account for most of an individual's resistence or susceptibility to AIDS.
"My sense is that the predominant issues for most people are some combination of genetics and the immune system," Buchbinder said. She has studied more than 6,000 gay and bisexual men in The City, including some who were infected with HIV 20 years ago and remain disease-free.
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