Researchers from the Institut national de la recherche scientifique (INRS) have made a significant breakthrough in finding a therapeutic approach to restore the effectiveness of immune cells in people infected with HIV-1. The study, published in the journal Autophagy, was led by doctoral student Hamza Loucif and Professor Julien van Grevenynghe, an expert in immunology and virology, and an awardee of the Banting Discovery Award (2017).

Most people infected with HIV-1 require daily antiretroviral therapy to control the infection, which often comes with significant side effects and does not fully restore the normal functioning of the immune system. However, a specific group of patients known as “elite controllers” are able to live with the infection without any drug intervention. This group of patients represents a unique model for detecting what needs to be improved for other patients, according to Professor van Grevenynghe.

The team of immunologists found that the energy metabolism within CD8 lymphocytes is what makes elite controllers stronger. Cells require energy produced in the mitochondria to protect the body and carry out their functions. However, this energy is not used effectively by treated patients, and the cells are weakened in their immune function due to a deregulation of the metabolism.

The research team demonstrated that CD8 lymphocytes can be “re-educated” using a soluble protein called interleukin-21 (IL-21) that optimizes their energy intake and immune function. This protein restores mitochondrial energy metabolism through a cell recycling process called autophagy. For elite controllers, the degradation of lipid reserves through autophagy, or lipophagy, is highly effective.

The findings of the study have tremendous therapeutic interest, as the protein already exists, and the fact that elite controllers exist is proof that one day we will be able to survive the infection without aggressive treatment. The cells could also respond better to vaccination and treatment with better energy efficiency.

The study also has the potential to impact other pathologies associated with persistent inflammation, such as cancer, diabetes, and even COVID-19 with lung inflammation.

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