HIV may well be the most studied virus of all time, yet the steps between its introduction into the body by sexual intercourse and an established infection still remain mysterious. Now, researchers report intriguing evidence that a little-understood protein may enable the virus to sneak behind the body's defenses. In addition to clarifying the mechanism of sexual transmission of HIV, the findings identify new targets for AIDS vaccines.
The new work, presented in two papers in the 3 March Cell, grew out of studies on dendritic cells, sentries that alert the immune system when invaders breach the body's borders. The researchers report that a protein called DC-SIGN carries HIV from dendritic cells in the mucosal lining of the cervix or rectum to remote lymph nodes. There, DC-SIGN hands HIV over to CD4+ T lymphocytes, the immune cells that the virus readily infects and destroys, eventually leading to AIDS.
The team, led by Yvette van Kooyk, a tumor immunologist at the University Medical Center St. Radboud in Nijmegen, the Netherlands, conducted test tube experiments to find out how HIV interacts with DC-SIGN. The protein binds tightly to the virus, they report, stabilizing it during the journey from mucosa to lymph nodes. This stabilization makes a huge difference: Without DC-SIGN, HIV lost its infectivity in less than a day. Protected by the protein, however, the virus could still infect CD4 cells after 4 days.
On a practical front, the findings may inform vaccine design. To date, many AIDS vaccine designers have aimed to elicit antibodies that interrupt the fusion of HIV to its CD4 cell targets. Now, they might seek to induce antibodies that block the binding of DC-SIGN to HIV. "It's very elegant work," says AIDS researcher Douglas Richman of the University of California, San Diego.