HIV envelope-CXCR4 signaling activates cofilin to overcome cortical actin restriction in resting CD4 T cells.
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.
Yoder
Alyson
A
Department of Molecular and Microbiology, George Mason University, Manassas, VA 20110, USA.
Yu
Dongyang
D
Dong
Li
L
Iyer
Subashini R
SR
Xu
Xuehua
X
Kelly
Jeremy
J
Liu
Juan
J
Wang
Weifeng
W
Vorster
Paul J
PJ
Agulto
Liane
L
Stephany
David A
DA
Cooper
James N
JN
Marsh
Jon W
JW
Wu
Yuntao
Y
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
D000199:Actins; D015704:CD4 Antigens; D051338:Cofilin 1; D015699:HIV Envelope Protein gp120; D019718:Receptors, CXCR4
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