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Vpr- and Nef-mediated downmodulation of MR lifts restriction of HIV in macrophages. Graphical depiction of our proposed model in which Vpr reduces transcription of MRC1, the gene that produces MR, and Nef binds to MR, to remove it from the cell surface. Low MR expression allows for high Env expression, efficient virion release, and formation of virological synapses between infected macrophages and uninfected CD4+ T cells.
