HIV-1 Fusion with CD4+ T cells Is Promoted by Proteins Involved in Endocytosis and Intracellular Membrane Trafficking
AbstractThe HIV-1 entry pathway into permissive cells has been a subject of debate. Accumulating evidence, including our previous single virus tracking results, suggests that HIV-1 can enter different cell types via endocytosis and CD4/coreceptor-dependent fusion with endosomes. However, recent studies that employed indirect techniques to infer the sites of HIV-1 entry into CD4+ T cells have concluded that endocytosis does not contribute to infection. To assess whether HIV-1 enters these cells via endocytosis, we probed the role of intracellular trafficking in HIV-1 entry/fusion by a targeted shRNA screen in a CD4+ T cell line. We performed a screen utilizing a direct virus-cell fusion assay as readout and identified several host proteins involved in endosomal trafficking/maturation, including Rab5A and sorting nexins, as factors regulating HIV-1 fusion and infection. Knockdown of these proteins inhibited HIV-1 fusion irrespective of coreceptor tropism, without altering the CD4 or coreceptor expression, or compromising the virus’ ability to mediate fusion of two adjacent cells initiated by virus-plasma membrane fusion. Ectopic expression of Rab5A in non-permissive cells harboring Rab5A shRNAs partially restored the HIV-cell fusion. Together, these results implicate endocytic machinery in productive HIV-1 entry into CD4+ T cells. View Full-Text
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Marin, M.; Kushnareva, Y.; Mason, C.S.; Chanda, S.K.; Melikyan, G.B. HIV-1 Fusion with CD4+ T cells Is Promoted by Proteins Involved in Endocytosis and Intracellular Membrane Trafficking. Viruses 2019, 11, 100.
Marin M, Kushnareva Y, Mason CS, Chanda SK, Melikyan GB. HIV-1 Fusion with CD4+ T cells Is Promoted by Proteins Involved in Endocytosis and Intracellular Membrane Trafficking. Viruses. 2019; 11(2):100.Chicago/Turabian Style
Marin, Mariana; Kushnareva, Yulia; Mason, Caleb S.; Chanda, Sumit K.; Melikyan, Gregory B. 2019. "HIV-1 Fusion with CD4+ T cells Is Promoted by Proteins Involved in Endocytosis and Intracellular Membrane Trafficking." Viruses 11, no. 2: 100.
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