Les plaquettes produites par des mégacaryocytes infectés provoquent des dysfonctionnements immunitaires dans le VIH/SIDA par son interaction avec les lymphocytes T CD4

Résumé du projet

The HIV/AIDS global epidemics remains a major public health challenge for more than 40 years. Enormous progress has been made on antiretrovirals, so that available antiretroviral therapy against HIV suppresses viral replication and restores the quality of life of the majority of individuals living with HIV. However, antiretroviral therapy does not cure HIV infection: once treatment is interrupted, the virus replication is resumed and rebound from infected cells that kept the virus dormant during treatment, and HIV infection progresses to immunodeficiency (AIDS). In addition, some individuals living with HIV do not properly reconstitute their immunological status despite adhering to the antiretroviral therapy, remaining in immunological failure. We have recently demonstrated that platelets, small cell fragments that circulate in the bloodstream and that participate in blood coagulation, do contain HIV that persists despite the therapy and are viral hideouts in individuals under treatment. Importantly, individuals with HIV in platelets are among those who remain in immunological failure, highlighting that platelets not only harbor persistent viruses but also, somehow, participate in impairing reconstitution of competent immunological status despite the therapy. Platelets are produced by a bone marrow-resident cell called the megakaryocyte, found infected by HIV-1 in the bone marrow of HIV-infected individuals treated by antiretroviral therapy.

Therefore, the main goal of the proposed “proof-of-concept” project is to demonstrate that platelets containing the virus have origin in infected megakaryocytes, inheriting from these mother cells the factors responsible for the platelet-mediated T cell immune failure. Platelets and megakaryocytes are largely neglected HIV hideouts that must be studied to develop improved antiretroviral therapies to treat this very sensitive group of individuals living with HIV, and also, and most importantly, to achieve complete eradication of HIV infection.