Vpr Promotes Macrophage-Dependent HIV-1 Infection of CD4+ T Lymphocytes

PLoS Pathogens

Zana Lukic¹  David R. Collins²  Jay Lubow²  Kathleen L. Collins³  Michael Mashiba⁴ 

[1] Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America;Department of Microbiology & Immunology, University of Michigan, Ann Arbor, Michigan, United States of America;Graduate Program in Immunology, University of Michigan, Ann Arbor, Michigan, United States of America;Medical Scientist Training Program, University of Michigan, Ann Arbor, Michigan, United States of America

关键词: T cells;    HIV-1;    Virions;    Macrophages;    Flow cytometry;    Lysosomes;    Lymphocytes;    Antibodies;   

DOI  :  10.1371/journal.ppat.1005054

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Vpr is a conserved primate lentiviral protein that promotes infection of T lymphocytes in vivo by an unknown mechanism. Here we demonstrate that Vpr and its cellular co-factor, DCAF1, are necessary for efficient cell-to-cell spread of HIV-1 from macrophages to CD4+ T lymphocytes when there is inadequate cell-free virus to support direct T lymphocyte infection. Remarkably, Vpr functioned to counteract a macrophage-specific intrinsic antiviral pathway that targeted Env-containing virions to LAMP1+ lysosomal compartments. This restriction of Env also impaired virological synapses formed through interactions between HIV-1 Env on infected macrophages and CD4 on T lymphocytes. Treatment of infected macrophages with exogenous interferon-alpha induced virion degradation and blocked synapse formation, overcoming the effects of Vpr. These results provide a mechanism that helps explain the in vivo requirement for Vpr and suggests that a macrophage-dependent stage of HIV-1 infection drives the evolutionary conservation of Vpr.

【 授权许可】

CC BY