HIV-1 Envelope Overcomes NLRP3-Mediated Inhibition of F-Actin Polymerization for Viral Entry.

Cell Rep

Cell Death and Aging Team, Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Laboratory of Molecular Radiotherapy, INSERM U1030, Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Université Paris Sud - Paris 11, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Department of Biomedical Sciences, University of the Pacific, Arthur A. Dugoni School of Dentistry, 155 Fifth Street, San Francisco, CA 94103, USA. Electronic address:

Published: September 2019

Purinergic receptors and nucleotide-binding domain leucine-rich repeat containing (NLR) proteins have been shown to control viral infection. Here, we show that the NLR family member NLRP3 and the purinergic receptor P2Y2 constitutively interact and regulate susceptibility to HIV-1 infection. We found that NLRP3 acts as an inhibitory factor of viral entry that represses F-actin remodeling. The binding of the HIV-1 envelope to its host cell receptors (CD4, CXCR4, and/or CCR5) overcomes this restriction by stimulating P2Y2. Once activated, P2Y2 enhances its interaction with NLRP3 and stimulates the recruitment of the E3 ubiquitin ligase CBL to NLRP3, ultimately leading to NLRP3 degradation. NLRP3 degradation is permissive for PYK2 phosphorylation (PYK2Y402) and subsequent F-actin polymerization, which is required for the entry of HIV-1 into host cells. Taken together, our results uncover a mechanism by which HIV-1 overcomes NLRP3 restriction that appears essential for the accomplishment of the early steps of HIV-1 entry.

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Source
http://dx.doi.org/10.1016/j.celrep.2019.02.095DOI Listing

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