Every bite, breath, or bug that enters your body passes through your gut. Luckily, your gut’s got a squad of immune cells called T cells to spot specific troublemakers. When any pathogens show up, the T cells pounce and neutralize the threat before it spreads.
But then comes HIV (human immunodeficiency virus), the master of disguise. While HIV can infect cells all over, it prefers to camp out in the gut, right inside those T cells. And unlike other areas, the immune system doesn’t sound the alarm here. It’s as if the virus has discovered a secret bunker.
Antiretroviral drugs for HIV are total game-changers, keeping the virus out of circulation. They keep HIV in check and help people live long, healthy lives.
But curing it? That’s the puzzle. Because HIV doesn’t fight, it hides. In some parts of the body, primarily the gut, HIV hunkers down and evades immune system attack.
Breakthrough antibody therapies offer hope for HIV treatment
In a new study published in Immunity, Yale researchers figured out how.
They discovered that the way our gut strengthens its immune cells also helps HIV settle in and stay hidden. The good news? This insight gives researchers a new target, one that could help flush HIV out from its safe zone and potentially clear it from the entire body.
They zoomed in on gut cells to figure out why HIV hides there so well. They found a key transcription factor, called BACH2, a kind of genetic switch that helps shape immune cells.
BACH2 gives T cells three important instructions: stay in the gut and not travel anywhere else, live long, basically, and stop throwing defensive, inflammatory weapons that could damage nearby healthy tissue.
These steps build a strong, lasting immune shield in the gut.
Ya-Chi Ho, MD, PhD, an associate professor of microbial pathogenesis at Yale School of Medicine and senior author of the study, said, “These findings make BACH2 an intriguing target for treating HIV. But there are challenges to that approach. BACH2 is found throughout the body, and it does perform a necessary function.”
“So we can’t just target BACH2 and get rid of all of these long-lasting T cells. We need to be specific and find a way to target only the T cells infected with HIV.”
“We’re using this approach to understand how HIV hides in other areas, such as in lymph nodes and cancer cells,” says lead author Yulong Wei, PhD, a postdoctoral associate in Ho’s lab whose bioinformatics background enabled the multidisciplinary approach that made the study possible.
The researchers are also investigating what controls BACH2, looking at neighboring gut immune cells and how they talk to the T cells, as well as how gut microbes influence that communication.
“We want to understand how all of these cells talk to each other,” says Ho. “This could yield other targets for clearing HIV.”
Journal Reference:
- Yulong Wei, Haocong Katherine Ma, Michelle E. Wong et al. Transcription factor BACH2 shapes tissue-resident memory T cell programs to promote HIV-1 persistence. Immunity. DOI: 10.1016/j.immuni.2025.07.022
