Vpr Promotes Macrophage-Dependent HIV-1 Infection of CD4+ T Lymphocytes.
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 inadeq...
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2015-07-01
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Series: | PLoS Pathogens |
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doaj-26d45abd8da046e6aa9758c1f90c54d22020-11-24T21:55:32ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742015-07-01117e100505410.1371/journal.ppat.1005054Vpr Promotes Macrophage-Dependent HIV-1 Infection of CD4+ T Lymphocytes.David R CollinsJay LubowZana LukicMichael MashibaKathleen L CollinsVpr 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.http://europepmc.org/articles/PMC4506080?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
David R Collins Jay Lubow Zana Lukic Michael Mashiba Kathleen L Collins |
spellingShingle |
David R Collins Jay Lubow Zana Lukic Michael Mashiba Kathleen L Collins Vpr Promotes Macrophage-Dependent HIV-1 Infection of CD4+ T Lymphocytes. PLoS Pathogens |
author_facet |
David R Collins Jay Lubow Zana Lukic Michael Mashiba Kathleen L Collins |
author_sort |
David R Collins |
title |
Vpr Promotes Macrophage-Dependent HIV-1 Infection of CD4+ T Lymphocytes. |
title_short |
Vpr Promotes Macrophage-Dependent HIV-1 Infection of CD4+ T Lymphocytes. |
title_full |
Vpr Promotes Macrophage-Dependent HIV-1 Infection of CD4+ T Lymphocytes. |
title_fullStr |
Vpr Promotes Macrophage-Dependent HIV-1 Infection of CD4+ T Lymphocytes. |
title_full_unstemmed |
Vpr Promotes Macrophage-Dependent HIV-1 Infection of CD4+ T Lymphocytes. |
title_sort |
vpr promotes macrophage-dependent hiv-1 infection of cd4+ t lymphocytes. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Pathogens |
issn |
1553-7366 1553-7374 |
publishDate |
2015-07-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC4506080?pdf=render |
work_keys_str_mv |
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