Actin-binding protein drebrin regulates HIV-1-triggered actin polymerization and viral infection.
HIV-1 contact with target cells triggers F-actin rearrangements that are essential for several steps of the viral cycle. Successful HIV entry into CD4(+) T cells requires actin reorganization induced by the interaction of the cellular receptor/co-receptor complex CD4/CXCR4 with the viral envelope complex gp120/gp41 (Env). In this report, we analyze the role of the actin modulator drebrin in HIV-1 viral infection and cell to cell fusion. We show that drebrin associates with CXCR4 before and during HIV infection. Drebrin is actively recruited toward cell-virus and Env-driven cell to cell contacts. After viral internalization, drebrin clustering is retained in a fraction of the internalized particles. Through a combination of RNAi-based inhibition of endogenous drebrin and GFP-tagged expression of wild-type and mutant forms, we establish drebrin as a negative regulator of HIV entry and HIV-mediated cell fusion. Down-regulation of drebrin expression promotes HIV-1 entry, decreases F-actin polymerization, and enhances profilin local accumulation in response to HIV-1. These data underscore the negative role of drebrin in HIV infection by modulating viral entry, mainly through the control of actin cytoskeleton polymerization in response to HIV-1.
From the Servicio de Inmunología, Instituto de Investigación Sanitaria de la Princesa, Hospital Universitario de la Princesa, 28006 Madrid, Spain.
Mónica
M
Gordón-Alonso
Vera
V
Rocha-Perugini
Susana
S
Álvarez
Ángeles
Á
Ursa
Nuria
N
Izquierdo-Useros
Javier
J
Martinez-Picado
María A
MA
Muñoz-Fernández
Francisco
F
Sánchez-Madrid
D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D015704:CD4 Antigens / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism* / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D018613:Microscopy, Confocal; D009479:Neuropeptides / Q000378:metabolism*; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D053586:Virus Internalization
D000199:Actins; D015704:CD4 Antigens; C527276:CXCR4 protein, human; D009479:Neuropeptides; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4; C053386:drebrins
Actin; Cxcr4; Cytoskeleton; HIV-1; Virus Entry