differential role of autophagy in cd4 t cells and macrophages during x4 and r5 hiv-1 infection微分作用cd4 t细胞和巨噬细胞的自噬在x4和r5 hiv - 1感染.pdfVIP

Differential Role of Autophagy in CD4 T Cells and Macrophages during X4 and R5 HIV-1 Infection 1. 1. ´ 1 1 2 Lucile Espert , Mihayl Varbanov , Veronique Robert-Hebmann , Sophie Sagnier , Ian Robbins , 1 1 1 Franc¸oise Sanchez , Virginie Lafont , Martine Biard-Piechaczyk * ´ ´ ´ 1 CPBS, UM1, UM2, CNRS, Institut de Biologie, 4, CS 69033, Montpellier, France, 2 Institut de genetique Moleculaire, Montpellier, France Abstract Background: HIV-1 can infect and replicate in both CD4 T cells and macrophages. In these cell types, HIV-1 entry is mediated by the binding of envelope glycoproteins (gp120 and gp41, Env) to the receptor CD4 and a coreceptor, principally CCR5 or CXCR4, depending on the viral strain (R5 or X4, respectively). Uninfected CD4 T cells undergo X4 Env-mediated autophagy, leading to their apoptosis, a mechanism now recognized as central to immunodeficiency. Methodology/Principal Findings: We demonstrate here that autophagy and cell death are also induced in the uninfected CD4 T cells by HIV-1 R5 Env, while autophagy is inhibited in productively X4 or R5-infected CD4 T cells. In contrast, uninfected macrophages, a preserved cell population during HIV-1 infection, do not undergo X4 or R5 Env-mediated autophagy. Autophagosomes, however, are present in macrophages exposed to infectious HIV-1 particles, independently of coreceptor use. Interestingly, we observed two populations of autophagic cells: one highly autophagic and the other weakly autophagic