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HIV resistance clue found

June 12, 2015 A small number of HIV-positive people mysteriously control the

Scanning electron micrograph of HIV particles infecting a human T cell.

Scanning electron micrograph of HIV particles infecting a human T cell. — National Institutes of Health
 

A small number of HIV-positive people mysteriously control the infection without getting drugs. They don't progress to AIDS, they remain outwardly healthy.

A new study has located what may be a crucial part of how these "elite controllers" keep HIV in check. They have a stronger response to HIV-1 infection from dendritic cells, a class of immune system cells that sense DNA from the virus. This stimulates production of T cells that target HIV, according to the study.

These elite controllers present a mystery, but also an opportunity for HIV researchers. If they can figure out how elite controllers naturally manage HIV disease through their own immune system, better therapies or a preventive vaccine might be developed.

A new study has located what may be a crucial part of that mechanism. Elite controllers have a stronger response to HIV-1 infection fromdendritic cells, a class of immune system cells that sense DNA from the virus. This stimulates production of T cells that target HIV, according to the study.

Dendritic cells are part of the innate immune system, which mounts a generalized response to infections. It works in tandem with theadaptive immune system, which specifically targets pathogens by means such as antibodies. Most work on developing HIV vaccines centers on improving antibody responses. However, in recent years more attention has been paid to the innate immune system, which is first in line to deal with infections.

HIV is a retrovirus, incorporating its genome into the genome of human cells. In this process, HIV, which is an RNA virus, transcribes its genome into DNA. This is when dendritic cells can detect HIV's presence by sensing the foreign DNA.

The study was led by a team from Massachusetts General Hospital, MIT and Harvard. It was published Thursday in the journal PLoS Pathogens.Dr. Xu G. Yu of MGH's Ragon Institute was senior author.

"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," said Yu, an associate professor of medicine at Harvard Medical School, in a statement.

A study published June 4 also focused on the role of dendritic cells in HIV detection. The study by Sanford-Burnham Medical Research Institute scientists identified a protein in dendritic cells that binds to DNA made by HIV, triggering an immune response.

Stimulating this immune activation as part of an HIV vaccine should help the vaccine work better, said study leader Sumit Chanda, director of the Immunity and Pathogenesis Program at Sanford-Burnham.

The new study is "provocative," Chanda said.

"Remarkably, the Yu group has shown that elite controllers are better and quicker at sensing HIV-1, and specifically HIV-1 DNA, which can lead to a controlling immune response," Chanda said by email. "Elite controllers can be equated with Typhoid Mary, as they are infected with the virus, but do not suffer from the disease."

"A subclass of sentinel immune cells, known as dendritic cells, can mount a more robust immune response to HIV-1 in these individuals, which both slows viral replication through a general (innate) immune response, as well as stimulates HIV-1-specific responses from CD8 T cells," Chanda said. "Lessons from understanding how elite controllers are able to control HIV-1 infection will be instrumental to developing new vaccine strategies and prophylactic therapies."

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