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Research unit director



Pathogenesis of Acquired Immunodeficiency Syndrome (AIDS)

Human AIDS is caused by HIV-1. There is no animal model of AIDS with HIV-1 and the best model remains infection of primates with SIV (simian immunodeficiency virus). Our laboratory is interested in developing models of HIV-1 induced AIDS in mice. To do so, we used the promoter of the human CD4 gene to express the HIV-1 genes in transgenic mice. Since CD4 is the receptor for HIV-1, the use of this receptor allowed expression of HIV-1 in the same cells as those normally infected in HIV-1 positive individuals. These CD4C/HIV transgenic mice develop a very severe disease with several phenotypes : thymic atrophy, preferential loss of CD4+ T cells, increase of CD8+ T cells, downregulation of cell surface CD4, interstitial pneumonitis, focal segmental glomerulosclerosis, cardiomyopathy, wasting, failure to thrive, weight loss, diarrhea, early death. All these phenotypes are very similar to those seen in AIDS patients. We showed that HIV-1 nef gene is mainly responsible for the appearance of these phenotypes and that paradoxically the T cells are constitutively activated and are hyperresponsive to stimulation through the T-cell receptor. The understanding of the pathogenesis of these different phenotypes remain an important goal of our laboratory.

Identification of novel immunogens capable of inducing anti-HIV broadly neutralizing antibodies.

Currently there is no vaccine against HIV-1. Elegant work in the last few years by many laboratories has identified broadly neutralizing antibodies (bnAb) in HIV-infected individuals and showed that passive immunization with these bnAb provides a very good protection against HIV-infection. Ideally, human vaccination against HIV-1 should generate bnAb very similar to those already identified. However, this represents a challenging task. Our laboratory is currently searching for Env-like molecules capable of eliciting bnAb when used as immunogens in mice and guinea pigs. The neutralization activity of mouse and guinea pig sera is assessed in vitro, using HIV-1 Env pseudotyped luciferase reporter viruses.

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