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HIV "elite controllers" starting to share their secrets

What are the mechanisms preventing viral progression in HIV "elite controllers"?  Researchers at the François Jacob Institute of Biology and their partners have shed light on some particularities of CD8+ T cells.

Published on 28 July 2017

​A small percentage of people infected with the human immunodeficiency virus (HIV) have a natural capacity to control the infection without treatment. In these rare patients, called "elite controllers", the viral load is kept under detection thresholds by the immune system. The specific mechanisms enabling this control of the infection remain mysterious, but CD8+ T lymphocytes appear to play a key role.

Indeed, in the ANRS SIC study, a team of researchers representing the Institut Pasteur, the CEA's François Jacob Institute, Paris-Descartes University, Paul Sabatier University, the AP-HP (greater Paris public hospital system) and Inserm succeeded in reproducing the controller effect in macaques infected with the simian immunodeficiency virus (SIV), the non-human-primate equivalent of HIV. The animals developed a CD8+ response against SIV in the days following infection. Initially, the response was poorly efficacious, but as the months went by, the CD8+ cells progressively optimized their ability to eliminate infected CD4+ cells. The acquisition of that ability coincided with viral control in the individual. Tests done on non-controllers showed a high viral load in lymph nodes, an aspect that appeared to impede the maturation of CD8+ T cells. 

In parallel, the authors of another study decrypted the characteristics of memory CD8+ T cells specific to HIV infection control. By analyzing the gene expression profile of more than a thousand of these cells individually, that team confirmed the presence of intrinsic differences between the cells of elite controllers and those of non-controllers. Specifically, the cells of non-controllers favor multiplication and use glucose as a source of rapid energy, whereas those of elite controllers favor survival, rapidly produce antiviral molecules, and mobilize several sources of energy, qualities that make them more adaptable and effective.

These results have been shared through a press release.

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