Back-Stabbing Molecule Aids HIV Infection

AIDS researchers thought they were studying a cellular ally in the fight against HIV. The molecule, called RANTES, seems to delay the onset of disease. But now RANTES turns out to be as two-faced as they come. Although researchers verified that the molecule slows down AIDS, they also discovered that it makes cells more likely to invite in HIV in the first place.

Three related molecules are known to inhibit HIV's spread from cell to cell. All of these, including RANTES, are immune system molecules called chemokines. Test tube studies showed that these molecules block the virus from infecting cells by both competing with HIV for entryways into T cells and somehow decreasing the number of receptors available for HIV to latch onto.

RANTES comes in a few genetically determined varieties. To find out whether these types influence a person's response to HIV, a team led by Philip Murphy of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, analyzed immune cell data from an ongoing study called the Multicenter AIDS Cohort Study (MACS) conducted in Chicago, Los Angeles, Washington, D.C., and Pittsburgh. MACS has been collecting blood samples from men at risk for HIV infection for more than 15 years. The team compared 404 men who became infected to 123 men who stayed HIV-free despite engaging in some of the same high-risk behaviors.

Murphy's team divided the men into two groups, depending on which version of the RANTES gene they carried. The group with the G4 variant took about 2 years longer, after becoming infected with HIV, to develop AIDS than did the group with the G1 variant, the team reports in the 1 December issue of the journal AIDS. In test tubes, the G4 variant of the gene produces more RANTES than the G1 version, supporting the idea that RANTES inhibits HIV's progression and thereby staves off illness. But the news isn't all good for men with the G4 variant: They are about twice as likely to become infected with HIV as G1 men.

It's strange that one version of a gene appears to protect from HIV infection but later allows the virus to proliferate. Murphy isn't sure how to interpret the finding, and he's not alone. "That is bizarre," says chemokine researcher Robert Gallo of the University of Maryland, Baltimore; "I don't know of any study before that showed a molecule inhibiting HIV and helping it at the same time. It's certainly a paradox."

Related sites
The Multicenter AIDS Cohort Study
Philip Murphy's home page

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