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Vpr Promotes Macrophage-Dependent HIV-1 Infection of CD4+ T Lymphocytes
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نویسنده
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collins d.r. ,lubow j. ,lukic z. ,mashiba m. ,collins k.l.
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منبع
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plos pathogens - 2015 - دوره : 11 - شماره : 7
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چکیده
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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. © 2015 collins et al.
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آدرس
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department of microbiology & immunology,university of michigan,ann arbor,mi, United States, department of microbiology & immunology,university of michigan,ann arbor,mi, United States, department of internal medicine,university of michigan,ann arbor,mi, United States, medical scientist training program,university of michigan,ann arbor,mi,united states,graduate program in immunology,university of michigan,ann arbor,mi, United States, department of microbiology & immunology,university of michigan,ann arbor,mi,united states,department of internal medicine,university of michigan,ann arbor,mi,united states,medical scientist training program,university of michigan,ann arbor,mi,united states,graduate program in immunology,university of michigan,ann arbor,mi, United States
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Authors
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