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

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Human immunodeficiency virus (HIV-1), the leading infectious killer worldwide, dysregulates the immune system primarily through infection and depletion of CD4+ T cells. The conserved HIV-1 Vpr protein has been previously shown to promote T cell infection and disease progression in an animal model; however, infection of primary CD4+ T cells in culture does not require Vpr, and its mechanism of action remains undefined. Here we show that Vpr promoted HIV-1 infection of CD4+ T cells by counteracting an antiviral restriction in infected primary macrophages. This restriction degraded HIV-1 in macrophages and impaired the formation of virological synapses–intercellular contact sites that facilitate efficient and immunoevasive viral transmission to T cells. Treatment of infected cells with the antiviral cytokine interferon-alpha induced this restriction even in the presence of Vpr, suggesting that Vpr prevents induction of an antiviral state in macrophages with consequences for viral spread to T cells. Our study provides mechanistic insight into the function of Vpr and the role of macrophage infection in HIV-1 pathogenesis, with implications for the development of improved treatment strategies.

Vyšlo v časopise: Vpr Promotes Macrophage-Dependent HIV-1 Infection of CD4 T Lymphocytes. PLoS Pathog 11(7): e32767. doi:10.1371/journal.ppat.1005054
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005054

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