Halting HIV spread in women

McElrath Lab findings on HIV-1 entry, infection may help block local spread and disease transmission
Dr. Julie McElrath
Co-author Dr. Julie McElrath said that her lab's findings provide "definitive insights into the initial events of HIV-1 infection in the human vagina" — information that can guide the design of strategies to block local HIV-1 transmission and spread. Photo by Susie Fitzhugh

Scientists in the Clinical Research Division have identified the primary targets of HIV-1 infection in the human vagina, findings that are likely to guide the development of new strategies to prevent HIV-1 transmission. The study appears in the February 2007 issue of the journal Immunity.

"The majority of HIV-1 infected individuals worldwide are women who acquire HIV infection following sexual contact," said study authors Drs. Florian Hladik and Julie McElrath. "Blocking HIV transmission and local spread in the female lower genital tract is key to prevent infection and ultimately to ease the pandemic."

Unique study model

Hladik and colleagues in the McElrath Lab developed a unique model system to study the precise mechanisms by which HIV-1 enters the lower reproductive tract of human females. The research team separated and removed the outer lining of vaginal cells, which serves as the first barrier to the virus, which permitted examination of immune cells that normally migrate out of the vaginal epithelium into deeper tissues shortly after HIV-1 exposure.

The researchers found that HIV-1 simultaneously enters two different types of intraepithelial cells associated with the immune system, Langerhans cells and CD4+ T cells. However, the path of entry and fate of infection was different for the two cell types, and, in contrast to previous studies, infection of CD4+ T cells does not appear to require passage of the virus from Langerhans cells.

Cell migration

Both Langerhans and CD4+ T cells can migrate out of the vaginal epithelium. Study findings suggest that CD4+ T cells may be principally responsible for local shedding of the virus in the vagina of women infected with HIV-1 while Langerhans cells may harbor viable virus for some time before spreading it to other cells.

These results reveal that it is necessary to consider mechanisms of viral entry into both types of cells when searching for an effective way to interfere with infection through the vaginal epithelium.

Grants from the National Institutes of Health, a Burroughs Wellcome Translational Research Award and the James B. Pendleton Trust supported the study. To learn more, visit www.immunity.com.

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