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Viruses 2019, 11(2), 100; https://doi.org/10.3390/v11020100

HIV-1 Fusion with CD4+ T cells Is Promoted by Proteins Involved in Endocytosis and Intracellular Membrane Trafficking

1
Department of Pediatric, Division of Infectious Diseases, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA 30322, USA
2
Functional Genomics Center, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA
3
Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
4
Children’s Healthcare of Atlanta, Atlanta, GA 30322, USA
*
Author to whom correspondence should be addressed.
Received: 4 January 2019 / Accepted: 23 January 2019 / Published: 25 January 2019
(This article belongs to the Section Animal Viruses)
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Abstract

The 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
Keywords: HIV; virus fusion; endocytosis; shRNA screen; cell fusion; membrane trafficking HIV; virus fusion; endocytosis; shRNA screen; cell fusion; membrane trafficking
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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.

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