Journal Article

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

Mashiba, Michael, Lubow, Jay, Collins, Kathleen L., Lukic, Zana, Collins, David R.

2015

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acquired immune deficiency syndrome / AIDS / CD4-Positive T-Lymphocytes - immunology / CD4-Positive T-Lymphocytes - virology / Colleges & universities / HIV / HIV-1 - immunology / Human immunodeficiency virus / Humans / Infections / Interferon / Interferon-alpha - metabolism / Lymphocytes / Macrophages - metabolism / Macrophages - virology / Medical research / Pathogenesis / Virion - metabolism / vpr Gene Products, Human Immunodeficiency Virus - immunology