BioEd Online

Researchers have developed a better understanding of how the HIV virus enters the female body during sex. The discovery could help to protect women and girls, who are more vulnerable than men to transmission of the virus during vaginal sex.

HIV attacks two types of cells in the skin of the human vagina, the US-based research team has found. The finding, reported in the journal Immunity¹, could be a crucial boost for scientists trying to design drugs and vaccines to guard against infection.

The researchers, led by Julie McElrath of the University of Washington in Seattle, wanted to know what happens when women are exposed to HIV through vaginal sex — the most common way for females to contract the virus.

Because the vagina's skin is the first barrier to the HIV virus, Florian Hladik, who is also at the University of Washington decided to look at vaginal skin removed during surgery. He used a chemical treatment to separate the outermost layer of vaginal skin from the underlying tissue. His team then exposed this layer to HIV viruses that had been tagged with a glowing dye. The team could then see which cells the viruses had infected.

Two at a time

Within two hours, HIV had attacked specialized immune cells called CD4+ T cells, and infected almost half of them. At the same time, the virus also infected other cells in the immune system called Langerhans cells, but it's not clear exactly how the virus does this.

This is important, because scientists have been unsure whether or not HIV directly infects CD4+ T cells in the vagina, says Ron Veazey, a pathologist at Tulane National Primate Research Center in Covington, Louisiana, who studies viruses similar to HIV in monkeys. "This is significant, because there's a lot of debate about what the initial targets of HIV infection are in the vagina," says Veazey. "She's demonstrated infection of both CD4+ T cells and Langerhans cells, and no one has demonstrated that before."

Knowing that the virus infects both T cells and Langerhans cells could help researchers to pick the best microbicides to protect women from HIV infection. Microbicides are creams or gels that aim to block HIV from invading a woman's body. But so far, three microbicide trials in women have failed.

One product, called Savvy, failed to protect women from the virus. The other two products actually appeared to increase women's risk of HIV infection. One of them, Ushercell, was pulled from clinical trials on 31 January this year because of these results.

A fresh approach

The new discovery could help researchers to avoid failures like these. The findings indicate that any effective microbicide must prevent HIV infection from entering both T cells and Langerhans cells, McElrath says.

"This [study] shows that when the female genital tract is exposed to HIV, it can pick between two different target cells to infect, so the best strategies will have to eliminate infection of both those cell types," McElrath says.

Scientists have designed microbicide candidates that do aim to block T cell infection. However, these products are still years away from large-scale clinical trials. The three microbicidal products that failed in clinical trials did not specifically target T cells, and neither do the three microbicide candidates still being tested in large human studies.