First evidence of the presence of HIV reservoirs in macrophages

Scientists from France recently discovered that macrophages located in the tissue of the urethra may play a much more significant role in the workings of HIV cell reservoirs, and that the number of these immune cells is surprisingly large. The results were published last week in Nature Microbiology.

According to experts, it is the existence of cellular reservoirs containing “latent” HIV that is the main obstacle to the elimination or cure of the infection.

The reservoirs are infected cells of the immune system, which, due to the action of antiretroviral drugs in the body, cannot reproduce the virus. However, as soon as the concentration of ART in the blood drops noticeably, HIV is activated again.

Most of the research in this area has focused mainly on T-lymphocytes, which, as previously thought, are the main immune cells that HIV targets.

In the framework of several works, scientists even made some attempts to “extract” “latent” HIV from reservoir cells by their reactivation. This approach consisted of two stages:

reactivation of latently infected cells with specific agents;

killing them by the patient’s immune system with new drugs.

However, to date, earlier attempts to eliminate HIV in this scenario have not been successful. According to experts, it may take years.

Unlike their colleagues, French scientists Morgan Bomsel and Yonatan Ganor from the Cochin Institute in Paris (Institute Cochin) decided to choose a different path.

They conducted a study of urethral tissue in twenty men with HIV who received antiretroviral therapy and had an undetectable viral load. All samples were obtained by scientists from people who have undergone sex change surgery. The researchers sought to identify and characterize the HIV reservoirs present in the tissue.

One of the key objectives of the work was to confirm the data that HIV genetic material, as well as a certain amount of virus strains that spread throughout the body after ARVT was discontinued, originates from a different, previously unrecognized cell reservoir other than a T cell.

Moreover, the task of specialists was to find evidence that macrophages are among the first immune cells affected by HIV during sexual transmission.

In the course of the work, researchers discovered the HIV genome in macrophages, and not in T-lymphocytes, as previously thought.

In addition, according to their data, contrary to expectations, after virus reactivation, it was produced only in macrophages, and not T lymphocytes.

Finally, microbiologists were able to characterize macrophages containing hidden reservoirs as a new subtype of immune cells, and noticed that their volume was significantly higher in groups of study participants.

In contrast to theories prevalent in scientific circles, according to which, as previously thought, HIV reservoirs are present only in T-lymphocytes, this study for the first time has shown that the main reactivated HIV reservoirs are located precisely in human tissue macrophages.

Although the authors of the paper called for a more thorough study of the described reservoirs of HIV in the macrophages of the mucous or lymphoid tissue, according to scientists, many of their colleagues are likely to be forced to rethink their strategies for fighting HIV.