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How "Elite Controllers" May Hold the Genetic Key to an HIV Cure

It’s a question long cloaked in mystery and hope: Why do some people with HIV never become sick?

Research published Thursday in the medical journal PLOS Pathogens offers more clues for piecing together the puzzle that may one day lead to an answer – and even a cure or a vaccine.

Scientists at Massachusetts General Hospital and the Ragon Institute examined what happens when HIV infects the dendritic cells of people with HIV who never progress and become sick. These people are known as “elite controllers.”

The research shows that dendritic cells in particular play a key role in mounting the successful immune response to HIV. Think of dendritic cells as computer hardware for the body – they come standard in everyone. Likewise, imagine T cells as software installed in each of us, actually doing the job of killing viruses. Without the hardware (dendritic cells) working properly, the software (T cells) can’t load and function properly.

Dendritic cells rush to the scene of infections. They patrol our body like infection police. When they spot trouble, they take information about the intruding infection to T cells, which we most often think of as the cells that do the tough job of beating back disease.

What they found was that in most people, dendritic cells immediately block HIV infection and keep it from reproducing. That may sound like good news, but in fact, the dendritic cells ultimately think they have done their jobs when that happens. In doing so, the dendritic cells don’t express the needed proteins that ultimately shine a light for the T cells, or CD 8 “killer” and CD4 “helper” cells, to go after the virus. The dendritic cells don’t kill the virus altogether, so it continues to circulate and replicate throughout the body, largely undetected by the immune system.

But in the dendritic cells of elite controllers, the virus actually is able to take hold because they lack a certain protein called SAMDH1 that would initially block viral replication. In doing so, the dendritic cells can then sound an alarm by expressing a protein called cGAS, alerting the T cells to recognize that HIV is present and to mount a powerful response.

“We are now focusing on fully understanding all the components required to trigger appropriate activation of dendritic cells in HIV infection, which may help to induce an elite-controller like, drug-free remission of HIV in a broader patient population,” explained Dr. Xu Yu. Yu is an associate professor of medicine at Harvard Medical School. The Ragon Institute is comprised of scientists form Massachusetts General Hospital, MIT and Harvard.

To read the news release from Massachusetts General Hospital about the research, click here. To examine the actual scientific paper, click here.