Autophagy and infectionsIRIM/CPBS -en
CPBS UMR 5236 CNRS UM1 UM2
1919 Route de Mende
34293 Montpellier Cedex 5 - Montpellier
Site web - -
The group is studying the role of autophagy during HIV-1 infection in the main virus target cells, namely the CD4+ T lymphocytes, the macrophages and the dendritic cells (DC). Our pioneering studies have demonstrated that HIV-1 envelope (Env) modulates autophagy in these cells. Interestingly, Env-mediated regulation of autophagy could result in sharp contrasted patterns, seemingly activated in non-infected bystander CD4+ T cells while strongly inhibited during productive infection. In infected myeloid DC and macrophages, autophagy flux was progressively and rapidly shut-down. Outstandingly, both observations could contribute to viral spread and establish the onset of HIV-mediated immunopathogenesis. Indeed, the former effect could explain the massive apoptosis of non-infected bystander CD4+ T cells while the latter correlated with a viral escape strategy favoring viral replication and transmission by counteracting autophagy-mediated antiviral immunity.
This work is supported by institutional funds from the Centre National de la Recherche Scientifique (CNRS) and the University of Montpellier, and grants from SIDACTION and the Agence Nationale de Recherches sur le SIDA (ANRS).
L. Espert, M. Denizot, M. Grimaldi, V. Robert-Hebmann, B. Gay, M. Varbanov, P. Codogno, M. Biard-Piechaczyk. Autophagy is involved in T cell death after binding of HIV-1 envelope proteins to CXCR4 (2006). J. Clin. Invest. 116: 2161-2172.
Blanchet, F.P., Moris, A., Nikolic, D.S., Lehmann, M., Cardinaud, S., Stalder, R., Garcia, E., Dinkins, C., Leuba, F., Wu, L., et al. (2010). Human immunodeficiency virus-1 inhibition of immunoamphisomes in dendritic cells impairs early innate and adaptive immune responses. Immunity 32, 654-669.