apobec3a is a specific inhibitor of the early phases of hiv-1 infection in myeloid cellsapobec3a是一种特定抑制剂的髓细胞中hiv - 1感染的早期阶段.pdfVIP

APOBEC3A Is a Specific Inhibitor of the Early Phases of HIV-1 Infection in Myeloid Cells 1,2,3 ´ 1,2,3 1,2,3 1,2,3 ´ Gregory Berger , Stephanie Durand , Guillaume Fargier , Xuan-Nhi Nguyen , Stephanie 1,2,3 4 1,2,3 1,2,3 1,2,3 Cordeil , Serge Bouaziz , Delphine Muriaux , Jean-Luc Darlix , Andrea Cimarelli * 1 Department of Human Virology, ENS-L, Lyon, France, 2 INSERM, U758, Lyon, France, 3 University of Lyon, Lyon I, IFR128, Lyon, France, 4 UMR 8015 CNRS, University Paris Descartes, Paris, France Abstract Myeloid cells play numerous roles in HIV-1 pathogenesis serving as a vehicle for viral spread and as a viral reservoir. Yet, cells of this lineage generally resist HIV-1 infection when compared to cells of other lineages, a phenomenon particularly acute during the early phases of infection. Here, we explore the role of APOBEC3A on these steps. APOBEC3A is a member of the APOBEC3 family that is highly expressed in myeloid cells, but so far lacks a known antiviral effect against retroviruses. Using ectopic expression of APOBEC3A in established cell lines and specific silencing in primary macrophages and dendritic cells, we demonstrate that the pool of APOBEC3A in target cells inhibits the early phases of HIV-1 infection and the spread of replication-competent R5-tropic HIV-1, specifically in cells of myeloid origins. In these cells, APOBEC3A affects the amount of vDNA synthesized over the course of infection. The susceptibility to the antiviral effect of APOBEC3A is conserved among primate lentiviruses, although the v