HIV's Helping Hand?

PARIS--A common virus may help the AIDS virus to infect some types of cells and wreak havoc on the immune system. The findings, reported in tomorrow's issue of Science,* imply a tighter symbiotic relationship between HIV and its possible ally--cytomegalovirus (CMV)--than previously imagined.

CMV, a member of the herpesvirus family that infects 80% of adults and almost all HIV-infected homosexual males, has long been a leading suspect as an AIDS cofactor. A team led by Marc Alizon at the Institut Cochin in Paris, in collaboration with Michel Seman at the University of Paris, set out to probe whether HIV may use a CMV protein called US28 to enter some types of cells. The protein is expressed in cells experimentally infected with CMV. US28 had previously been shown to act as a docking point, or receptor, for the same immune system signaling molecules, called chemokines, that bind to CCR5, a receptor used by HIV strains that dominates during the early phases of infection.

To determine whether US28 might act as HIV's accomplice, the French group inserted the US28 gene into a human cell line that HIV does not normally infect. Alizon's group then exposed these cells, which express the US28 protein on their surfaces, to various HIV strains. In these and related experiments, Alizon's team found that US28-bearing cells were easily infected by HIV strains that normally use the human chemokine receptor CCR5, and somewhat less easily by strains that use another human receptor, CXCR4.

"The results are provocative and potentially important for HIV pathogenesis," says Philip Murphy, a chemokine receptor expert at the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland. Adds David Posnett, an immunologist at Cornell University Medical College in New York who has studied CMV: "I'm just wondering what this all means in real life."

Indeed, it is not yet clear whether the French group's results, which are restricted to laboratory cell lines, are relevant to HIV-infected people. "There is a total lack of information about when, where, and how much of US28 is expressed in people infected with CMV," says Murphy. Thus experts will continue to debate whether CMV is merely an opportunistic organism taking advantage of the immune suppression caused by HIV, or a true partner in destroying the immune system.

*For more details, Science Online subscribers can link to the full text of the Report.

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