Intriguing biomarker identifies hidden HIV reservoirs to kill them

Scientists have identified a biomarker at the surface of the immune cells CD4 T, which could help them isolate hidden HIV reservoirs in the body. Their findings represent an important first step towards discovering a potential cure.

HIV-positive patients can now take antiretroviral therapy (ART), a combination of medications that suppress viral production and spread. While it does not "cure" them, ART can allow them to live a longer, healthier life. Along with better prevention, these drugs are credited to have save 7.8 million lives over the last 15 years.

However, if people discontinue their treatment, HIV re-emerges. Dormant versions of the virus indeed hide in cellular reservoirs, ready to start replicating as soon as patients go off their drugs. This is one of the most important challenges to efficiently treating HIV-infected individuals today and to finding a cure.

CD4 T cells are the predominant type of immune cells that can harbour a reservoir of dormant HIV but there is no way to destroy it at present.

"Today, we don't know how to identify the virus' latent reservoirs. We don't know how to isolate and purify them because, before our study, we had no biomarkers that distinguish them from their non-infected counterparts", Monsef Benkirane, from the CNRS and the University of Montpellier (France), one of the authors of the study published in Nature, told IBTimes UK.

A protein at the surface

Benkirane and his colleagues used the knowledge they had gained from previous research to generate latent HIV cellular reservoirs and to study them in vitro. These were infected but dormant cells — they were not activated or proliferating as are most CD4 T cells propagating high levels of HIV.

The idea was to find a biomarker on these cells which would not be expressed on the surface of non-infected cells. The researchers identified one – a protein called CD32a.

"I've always said, 'I can't believe that cells that have been infected did not keep a memory of the infection'. Here, we identified CD32a on the surface of the cellular reservoir. This is a good news, because being on the surface means that it will be easier to target the biomarker with antibodies", Benkirane said.

This could be a first tentative step to find a cure against HIV, since the impossibility to destroy latent reservoirs is currently the major obstacle standing in the way. The researchers think it might be possible to use CD32a to selectively target these rare, latent infected cells.

"There is a strategy known as "kill', which is about directly targeting and eliminating the HIV reservoir cells. This strategy has been on standby because we didn't have the biomarker to identify them. Our work makes it possible to implement the "Kill" strategy", Benkirane added.

However, before any of this can happen, it will be equally to answer other questions that remain regarding CD32a such as what is the function of this biomarker and whether it is specific to an HIV infection and to CD4 T cells. Scientists are also very intrigued by the fact that this biomarker appears to be linked to the cell's state of quiescence (its state of inactivity), and are keen to learn more about why that is.