HIV Exploits Environment of Mucosal Tissues to Spread Infection

Fibroblasts increase HIV infection of CD4 T cells, according to a study published in PLOS Pathogens. The findings may lead to new treatment methods for preventing HIV transmission.

Breaches in the mucosa allows HIV to freely bypass the intestinal tracts protective layer to infect immune cells.

The investigators used an experimental system that models the mucosa and surrounding tissues. The results of the study showed that the connective tissues cells fibroblasts increased HIV infection.

One method the fibroblasts used was transporting the virus to the body’s immune cells through the process of trans-infection, according to the authors.

“We were interested in understanding how cells commonly found in mucosal tissues affect the ability of HIV to infect immune cells,” said senior author Nadia Roan, PhD. “We discovered that, remarkably, mucosal fibroblasts could potential increase how well HIV infected immune cells. Knowing how this occurs at the molecular levels can help us find new ways to fight the virus.”

For the study, the investigators examined mucosal fibroblasts from the cervix, uterus, intestines, foreskin, and male urethra. The fibroblasts from all of the tissues were found to increase HIV infection by trans-infection, and by making the immune cells more prone to infection by the virus.

In future research, the investigators plan to examine precisely how mucosal fibroblasts cause immune cells to become more easily infected. The authors hope this will lead to new targets for HIV prevention.

The investigators also tested epithelial cells, which line the mucosa and allow helpful substances to pass through tissues in the body and act as a barrier against harmful substances. Contrastingly, the authors found that the epithelial cells secreted high levels of antiviral proteins that inhibit infection.

“Our work suggests that breaches in the mucosa allow HIV to bypass an antiviral environment to access fibroblasts, which in turn boost levels of HIV infection in CD4 T cells,” said senior investigators Warner Greene, MD, PhD. “Knowing the specific cells that allow HIV to take advantage of breaches in our defenses will enable us to find better ways to limit HIV transmission rates.”