Even though we’re now some four decades into the HIV epidemic, researchers still don’t seem to appreciate some pretty basic elements when it comes to how cisgender women contract HIV. In particular, the mechanisms behind HIV acquisition via male-to-female sex are poorly understood. Thankfully, new findings may help unravel how HIV impacts women both at the moment of contraction and long after transmission occurs.

Researchers previously discovered that T cells aren’t present in the outermost portions of intimate regions of the female anatomy (the outer layer of skin cells), so scientists still weren’t exactly sure how women were acquiring HIV.

A new study published in The Journal of Clinical Investigation suggests that vaginal epithelial dendritic cells may be where all the action occurs, being both where the infection may originally take place and where the virus may find reservoirs during treatment.

Dr. Manish Sagar, principal investigator of the study and an infectious disease specialist at Boston Medical Center, and his team focused on vaginal epithelial dendritic cells for two reasons. “First, HIV can replicate in these cells,” Dr. Sagar explains. “Second, these cells are located in the outermost part of vagina. While HIV primarily replicates in T cells, T cells are not present in the outermost part of the vaginal mucosa, so they do not have direct exposure to an incoming virus. Thus, T cells are probably not the first cell infected during sexual exposure. Vaginal epithelial dendritic cells are most likely to encounter HIV when women are exposed to the virus during sexual contact. We think these are probably the first cells infected because of these two reasons.”

With so much focus on T cells, it’s easy to overlook other ways that HIV can replicate. After viral suppression occurs on HIV treatment (in which the virus becomes so suppressed that it reaches undetectable levels — making it virtually impossible to transmit), it can still hide deep inside viral reservoirs from which it can ultimately rebound.

“Our finding that HIV DNA is found in vaginal epithelial dendritic cells suggest that these cells are also one reason why HIV can persist forever even with effective treatment,” Sagar says.

“The basic cellular biology of male-to-female transmission is poorly understood,” Sagar adds, but the behavior of the virus remains the same in both men and women. Still, he believes his research could lead to new treatments, particularly HIV prevention drugs aimed at women who have sex with men. “Identifying the first infected cells opens new avenues into developing novel strategies to prevent HIV acquisition.”

Understanding the relationship between vaginal epithelial dendritic cells and HIV is key to the possible introduction of such investigational medications.