title: HIV envelope-CXCR4 signaling activates cofilin to overcome cortical actin restriction in resting CD4 T cells.
abstract: Binding of the HIV envelope to the chemokine coreceptors triggers membrane fusion and signal transduction. The fusion process has been well characterized, yet the role of coreceptor signaling remains elusive. Here, we describe a critical function of the chemokine coreceptor signaling in facilitating HIV infection of resting CD4 T cells. We find that static cortical actin in resting T cells represents a restriction and that HIV utilizes the Galphai-dependent signaling from the chemokine coreceptor CXCR4 to activate a cellular actin-depolymerizing factor, cofilin, to overcome this restriction. HIV envelope-mediated cofilin activation and actin dynamics are important for a postentry process that leads to viral nuclear localization. Inhibition of HIV-mediated actin rearrangement markedly diminishes viral latent infection of resting T cells. Conversely, induction of active cofilin greatly facilitates it. These findings shed light on viral exploitation of cellular machinery in resting T cells, where chemokine receptor signaling becomes obligatory.
authors.affiliation: Department of Molecular and Microbiology, George Mason University, Manassas, VA 20110, USA.
authors.forename: Alyson
authors.initials: A
authors.lastname: Yoder
authors.forename: Dongyang
authors.initials: D
authors.lastname: Yu
authors.forename: Li
authors.initials: L
authors.lastname: Dong
authors.forename: Subashini R
authors.initials: SR
authors.lastname: Iyer
authors.forename: Xuehua
authors.initials: X
authors.lastname: Xu
authors.forename: Jeremy
authors.initials: J
authors.lastname: Kelly
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.forename: Weifeng
authors.initials: W
authors.lastname: Wang
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Vorster
authors.forename: Liane
authors.initials: L
authors.lastname: Agulto
authors.forename: David A
authors.initials: DA
authors.lastname: Stephany
authors.forename: James N
authors.initials: JN
authors.lastname: Cooper
authors.forename: Jon W
authors.initials: JW
authors.lastname: Marsh
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D015704:CD4 Antigens; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002478:Cells, Cultured; D051338:Cofilin 1 / Q000737:chemistry / Q000378:metabolism*; D006678:HIV; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015658:HIV Infections; D006801:Humans; D008969:Molecular Sequence Data; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000199:Actins; D015704:CD4 Antigens; D051338:Cofilin 1; D015699:HIV Envelope Protein gp120; D019718:Receptors, CXCR4
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