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The main weapon of HIV, which at the moment makes it invincible, is its ability to hide within the body. This is what makes up the so-called viral reservoir, which is made up of viruses that are introduced into cells that remain dormant and that, due to their inactivity, cannot be detected or destroyed by the immune system. Now, a study co-led by the Vall d'Hebron Research Institute (VHIR) and in which the IrsiCaixa AIDS Research Institute has also collaborated, gives new data on the reservoir.
The study proves that the molecule CD32 is a marker of the cells that are starting the generation of new viruses and not a marker of latency, as had been concluded a year ago by a research published in the journal Nature. That is, CD32 appears in active cells where HIV gene expression usually occurs. Thus, if an infected cell has CD32 in its membrane, it means that it is expressing - or in other words, producing - virus.
The result has been proven not only in circulating cells in the blood, but also in tissues of the immune system. "Using state-of-the-art techniques, we have been able to determine that CD32 is found mainly in cells actively infected with HIV, and not in dormant cells as previously believed. In addition, we have observed this in both blood samples and lymph nodes, one of the main hiding places of the virus," explains Dr. María José Buzón, leader of the HIV Translational Research line of the Vall d'Hebron Infectious Diseases group, and one of the leading authors of the study. The Wistar Institute (Philadelphia) and the University of Pennsylvania are the other centres that co-lead the work.
"From the outset, these conclusions may seem to be bad news - argues Javier Martínez-Picado, ICREA research professor at the IrsiCaixa Institute for AIDS Research and professor at the University of Vic - Central University of Catalonia-, but we must bear in mind that, in science, negative results have a tremendous value, since they allow us to limit the way. Knowing where not to go means being one step closer to the right route."
Dr. Buzón and Dr. Martínez-Picado are among the 30 members of the BEAT-HIV consortium, made up of institutions that work together with governments, civil society and industry to design immunotherapies against HIV. One of the main objectives of the consortium is precisely to describe all the possible hiding places of the virus in the organism, in order to design therapeutic strategies to eliminate it.
One in a million
Current treatments act against the virus at various stages of infection, for example by preventing its entry into the CD4 T-lymphocyte or the action of the enzyme that allows new viruses to form. The immune system also acts against HIV, destroying the cells that generate virions and thus show that they have been infected. But despite this, the virus still remains dormant in a small proportion of CD4 T-lymphocytes, about one per million. These cells may remain inactivated for months or even years, but as soon as they wake up from their latency the virus begins to replicate and spread back into the body.
It has also been described that even if antiretroviral treatment is taken, the existence of the reservoir keeps the immune system constantly alert, causing inflammation and damage to organs and tissues. For all these reasons, the reservoir has been under study for 20 years, but the mechanisms by which it is governed are still unclear. Hence the importance of the study published in Science Translational Medicine.
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