title: Vpr Promotes Macrophage-Dependent HIV-1 Infection of CD4+ T Lymphocytes.
abstract: 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.
authors.affiliation: Department of Microbiology & Immunology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: David R
authors.initials: DR
authors.lastname: Collins
authors.affiliation: Department of Microbiology & Immunology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Jay
authors.initials: J
authors.lastname: Lubow
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Zana
authors.initials: Z
authors.lastname: Lukic
authors.affiliation: Medical Scientist Training Program, University of Michigan, Ann Arbor, Michigan, United States of America; Graduate Program in Immunology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Mashiba
authors.affiliation: Department of Microbiology & Immunology, University of Michigan, Ann Arbor, Michigan, United States of America; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America; Medical Scientist Training Program, University of Michigan, Ann Arbor, Michigan, United States of America; Graduate Program in Immunology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Collins
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000821:virology*; D014771:Virion / Q000378:metabolism; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D016898:Interferon-alpha; D054325:vpr Gene Products, Human Immunodeficiency Virus