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HIV Controllers Are Starting to Unravel Their Secrets

What are the mechanisms of HIV control in individuals known as "controllers"? Researchers at the François-Jacob Institute and their partners have highlighted the peculiarities of CD8+ T cells.

Published on 28 July 2017

The term "controller" refers to patients infected with the Human Immunodeficiency Virus (HIV) who have the natural ability to handle the infection without treatment. In these rare cases, the viral load is controlled by the immune system, and blood tests are unable to detect measurable levels. Currently, the precise mechanisms involved in the response to infection remain unsolved. Yet CD8+ T-cells seem to play a major role in how the immune system controls the disease.

In an ANRS SIC study conducted by Institut Pasteur, the CEA François-Jacob Institute and Université Paris-Descartes and Paul Sabatier in Toulouse, as well as the University Hospital of Île-de-France and Inserm, scientists have reproduced the "controller" effect in macaques infected with simian immunodeficiency virus (SIV, the HIV equivalent in non-human primates). The animals developed a CD8+ response against SIV within days following infection. This response was initially ineffective, then over the next few months, the CD8+ cells acquired an optimal ability to eliminate infected CD4+ cells. The acquisition of this ability was concomitant with the control of the virus in the entire organism. Tests in non-controller individuals show a high amount of virus in the ganglia, which appears to interfere with CD8+ T-cell maturation.

Concurrently, another study has deciphered the characteristics of HIV-specific memory CD8+ T-cells associated with infection control. By individually analyzing the gene expression profile of more than 1,000 cells, the researchers were able to confirm intrinsic differences between controller and non-controller cells. While the cells of non-controller patients are programmed to multiply and use glucose as a fast energy source, the cells of controllers are programmed to survive and rapidly produce antiviral molecules using multiple energy sources. These characteristics make them more adaptable and efficient.

This result was the subject of a press release.

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