Gene Defect Fails to Block HIV

AIDS researchers were encouraged last year when they found that people with a specific genetic defect appeared to be protected from infection by HIV. But a new finding, reported in the March issue of Nature Medicine, indicates that this protection is not absolute. The report serves as a warning that nobody is completely safe from infection.

Robyn Biti, Graeme Stewart of Westmead Hospital in Sydney, Australia, and colleagues report that they have found an HIV-infected homosexual man whose white blood cells contain a defective copy of a critical surface protein, called CCR5, that the virus uses to gain entry into the cells. Previous studies in nearly 3000 HIV-infected people had failed to uncover a single person who had inherited copies of the mutated gene that produces the CCR5 protein from both parents. "Up until this paper, many people thought it would be a `never' event," says Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases (NIAID). "I'm not surprised that it happens, and I'm sure this is not the only one we'll see."

Last year, researchers at NIAID and elsewhere solved a decade-long mystery when they found that HIV uses a second set of proteins to gain entry into immune cells. Besides docking to white blood cell receptors called CD4, the scientists found that HIV also enters cells via receptors--such as CCR5--normally reserved for immune messengers called chemokines. Researchers found that some people who had been repeatedly exposed to HIV but remained uninfected had two copies of a defective CCR5 gene. The finding suggested that this flaw offered strong protection from the virus.

Stewart, an immunologist, says that rather than rebutting the earlier work, the new data simply add complexity to the story. CCR5 should remain "a very important target for vaccines and drugs," he says, noting that they have found only one person with the double CCR5 defect in 300 people studied so far. But the one case is disturbing nonetheless: The subject--who first tested positive for HIV 5 years ago--already is showing signs of immune damage from HIV. The Australian team is now attempting to identify the strain of the man's virus to see how it compares to other HIV strains that require CCR5 to slip into immune cells.

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