Just in time forWorld AIDS DayIn 2021, scientists identified the key role of the transcription factor RORC2 in HIV infection. The molecule attaches to parts of the virus's genome but does not prevent it from replicating. With research, the authors of the new study will now try to provide a potential treatment option that could stop virus replication.
New therapeutic target identified against HIV infection
During the viral infection, the human immunodeficiency virus hides in immune cells called CD4+ T cells. These absorb it and enable it to continue to multiply. Among such T cells, Th17 cells, which are responsible for defense and protection of the integrity of mucous membranes, are particularly permissive. This is because they allow the virus to replicate and are actually involved in its persistence, and so far there has been no explanation for this phenomenon. The new study results show that RORC2, the molecule that regulates the immune function of Th17 cells, promotes the expression of the virus within these cells by binding to a specific region of the viral genome. In the laboratory, the research team managed to inhibit its effect using small pharmacological molecules. In this way, they were able to prevent the HIV virus from multiplying in the CD4+ T cells of healthy participants.
In the same type of cells, this time from people who had been infected with HIV and were receiving antiretroviral therapy, the researchers managed to limit virus expansion. This completely new proof of concept implies that the virus could even use RORC2 to ensure its survival. In the battle of the immune system, these cells are among the first victims of HIV. Their loss leads to a violation of the integrity of the intestinal mucosal barrier and leads to systemic inflammation. The surviving Th17 cells contribute to the persistence of the HIV reservoir by allowing the virus to replicate. This is a chronic inflammation that leads to complications not directly related to AIDS. The authors' goalthis studyis now to limit the remaining viral transcription in Th17 cells. Currently, their priority is to test the antiviral effects of RORC2 inhibitors in a preclinical model.
