Actin-binding protein drebrin regulates HIV-1-triggered actin polymerization and viral infection

Actin-binding protein drebrin regulates HIV-1-triggered actin polymerization and viral infection

Data de publicació online: 07/08/2013 Revista: The Journal of Biological Chemistry

Abstract:

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 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.

 

Autors: Gordón-Alonso M, Rocha-Perugini, Álvarez S, Ursa Á, Izquierdo-Useros N, Martinez-Picado J, Muñoz-Fernández MA, Sánchez-Madrid F.

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