WASHINGTON-It takes more than CD4 for HIV to take command of cells.
Discoveries from five labs reveal that one or more chemokine receptors must be on lymphocytes and macrophages before HIV can inject its RNA.
In patients who seem to be HIV-resistant despite repeated exposure to the virus, the CKR5 chemokine receptor is likely to be missing or genetically altered, says NYU’s Dr. Dan Littman.
Chemokines are “chemotactic cytokines” that mediate inflammation. CKR5 is a normal G protein-coupled receptor that twines in and out of cell membranes.
“Amazingly, HIV-1 has subverted this normal cell-surface protein for its own use,” says Dr. Nathaniel Landau of New York’s Aaron Diamond AIDS Research Center. “We believe that this protein is crucial for viral replication and transmission in vivo.”
But that doesn’t mean CD4 is irrelevant. NIH’s Dr. Edward Berger- who discovered the first HIV coreceptor, fusin, this spring-says HIV apparently seeks out CD4-bearing cells hoping to find the right chemokine coreceptor.
A link between chemokines and HIV was first elucidated late in 1995 by the University of Maryland’s Dr. Robert Gallo, who said they appeared to be the postulated mystery agents associated with high counts of helper T cells and long-term survivors. Appearance of fusin-seeking HIV strains may coincide with the transition to symptomatic disease, Dr. Berger says, perhaps explaining the drop-off in CD4s in AIDS.
His lab, with four others, showed that some HIV strains can’t insert their genomes into CD4-bearing T cells if CKR5 is missing. And in vitro studies at Aaron Diamond show that chemokines block entry of such strains into CKR5-bearing T cells. -Joe R. Neel
WASHINGTON-It takes more than CD4 for HIV to take command of cells.
