HIV Clues Point to Potential Preventive Therapy

New "snapshots" of HIV in the act of binding to two proteins that facilitate infection of T cells may lay the groundwork for future therapies, according to Dr. Bill Weis of Stanford University and colleagues in the December 7th issue of Science (2001;294:2163-2166).

The researchers studied two molecules, called DC-SIGN and DC-SIGNR that appear to enhance the efficiency with which HIV infects T cells. Because HIV targets the immune system's T cells, understanding the interaction at the molecular level should help in preventing HIV infection.

"The particular cells that have DC-SIGN on their surface are found in these tissues lining the cervix, uterus and rectum, which of course are where sexually transmitted HIV will be encountered," Weis told Reuters. "Likewise," Weis said, "the other molecule, DC-SIGNR, is found on the lining of capillaries in the lymph nodes and placenta" -- which may account for how the virus crosses from mother to fetus.

Using x-ray crystallography to visualize the interaction between HIV and DC-SIGN and DC-SIGNR, the investigators found that the molecules both have regions that recognize specific parts of HIV -- specifically a type of carbohydrate attached to the surface protein of the virus. The interactions "represent a potential target for anti-HIV therapy," Weis said. "We hope to use this information in collaboration with chemists to design therapeutic agents that would block HIV's ability to attach to these receptors."

The therapy that could be developed would be preventative and not an HIV treatment. "It may turn out to be a potentially useful target to slow infections already present," he noted, although that possibility "doesn't seem likely."

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