Unraveling the Mechanisms of Male-to-Female HIV Transmission

By Jeffrey Laurence, M.D.

HIV particles infecting a human T cell. Source: National Institute of Allergy and Infectious Diseases (NIAID)

One key to ending the AIDS pandemic will be an effective biomedical intervention—such as a vaccine or microbicide—to prevent the acquisition of the virus. An important step in the process of identifying suitable candidates is to derive a detailed understanding of the cellular mechanisms by which HIV is transmitted sexually. A key component in rectal transmission of the virus is the dendritic cell (DC).  Four years ago, Dr. Phillip Smith and colleagues at the University of Alabama at Birmingham found that DCs in the intestinal mucosa rapidly capture HIV on their long tentacle-like membrane structures, then directly transmit it to cells capable of becoming infected, such as the T cells of the blood and gut.

With amfAR funding, Dr. Smith and associates expanded this work to explore the mechanisms involved in penile-vaginal transmission of HIV. Writing in the July issue of the Journal of Virology, they report on a DC-based process in vaginal mucosa very similar to what they had documented in the intestines.

First, Smith’s team characterized DCs in samples obtained from the vaginal tissue of healthy women not receiving hormone therapy. Supporting the possibility that the DCs were likely viral carriers, they found high levels of expression of all three critical HIV receptors on the cells’ surface: CD4, CCR5, and CXCR4, along with a receptor typical of DCs, DC-SIGN.

Next, using tissues grown in the lab, the researchers showed that vaginal DCs could capture HIV and transport it through vaginal mucosa to infect vaginal and blood T cells. They were the only vaginal cells capable of doing so. Together, these findings suggest that vaginal DCs could play a key role in HIV transmission during heterosexual sex. Studies by the Smith group of the mechanics of rectal and vaginal transmission of HIV should help facilitate the development of methods to block all sexual transmission of the virus.

Dr. Laurence is amfAR’s senior scientific consultant.