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

• Main Authors: David R Collins, Jay Lubow, Zana Lukic, Michael Mashiba, Kathleen L Collins
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2015-07-01
• Series: PLoS Pathogens
• Online Access: http://europepmc.org/articles/PMC4506080?pdf=render

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.