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000282595 1001_ $$00000-0002-6526-4133$$aLaliberté, Alexandre$$b0
000282595 245__ $$aNef stabilizes actin to prevent HIV-1 sensing by RIG-I-like receptors.
000282595 260__ $$a[London]$$bSpringer Nature$$c2025
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000282595 520__ $$aSensing of viral pathogens by RIG-I-like receptors (RLRs) requires their priming via dephosphorylation mediated by the protein phosphatase 1 regulatory subunit 12 C (R12C), which is activated upon virus-induced actin rearrangements. Here, we show that the HIV-1 accessory protein Nef prevents R12C-mediated RLR priming, thereby suppressing viral sensing. HIV-1 variants containing single point mutations in Nef (F/R191A) that ablate its ability to bind the actin-modulating kinase PAK2 trigger increased interferon (IFN) responses in primary CD4+ T cells, macrophages, and dendritic cells. Neutralization of IFN suppresses innate immune activation and enhances the replication of Nef-mutated HIV-1. We further demonstrate that HIV-1 encoding Nef F/R191A is sensed by MDA5 after proviral integration in an R12C-dependent manner. Mechanistically, PAK2 binding by Nef promotes actin repair and stabilization, thereby preventing re-localization of R12C to MDA5 and RIG-I and their subsequent dephosphorylation. Our data identify Nef as an antagonist of actin-R12C-mediated RLR priming, enabling HIV-1 to escape immune control.
000282595 536__ $$0G:(DE-HGF)POF4-351$$a351 - Brain Function (POF4-351)$$cPOF4-351$$fPOF IV$$x0
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000282595 650_7 $$2NLM Chemicals$$anef Gene Products, Human Immunodeficiency Virus
000282595 650_7 $$2NLM Chemicals$$aActins
000282595 650_7 $$2NLM Chemicals$$aReceptors, Immunologic
000282595 650_7 $$0EC 3.6.4.13$$2NLM Chemicals$$aDEAD Box Protein 58
000282595 650_7 $$2NLM Chemicals$$anef protein, Human immunodeficiency virus 1
000282595 650_7 $$0EC 2.7.11.1$$2NLM Chemicals$$ap21-Activated Kinases
000282595 650_7 $$0EC 3.6.1.-$$2NLM Chemicals$$aRIGI protein, human
000282595 650_7 $$0EC 3.6.4.13$$2NLM Chemicals$$aInterferon-Induced Helicase, IFIH1
000282595 650_7 $$0EC 2.7.11.1$$2NLM Chemicals$$aPAK2 protein, human
000282595 650_7 $$0EC 3.6.1.-$$2NLM Chemicals$$aIFIH1 protein, human
000282595 650_7 $$0EC 3.1.3.16$$2NLM Chemicals$$aProtein Phosphatase 1
000282595 650_7 $$09008-11-1$$2NLM Chemicals$$aInterferons
000282595 650_2 $$2MeSH$$aHumans
000282595 650_2 $$2MeSH$$aHIV-1: immunology
000282595 650_2 $$2MeSH$$aHIV-1: genetics
000282595 650_2 $$2MeSH$$anef Gene Products, Human Immunodeficiency Virus: metabolism
000282595 650_2 $$2MeSH$$anef Gene Products, Human Immunodeficiency Virus: genetics
000282595 650_2 $$2MeSH$$anef Gene Products, Human Immunodeficiency Virus: immunology
000282595 650_2 $$2MeSH$$aActins: metabolism
000282595 650_2 $$2MeSH$$aReceptors, Immunologic
000282595 650_2 $$2MeSH$$aDEAD Box Protein 58: metabolism
000282595 650_2 $$2MeSH$$aHIV Infections: immunology
000282595 650_2 $$2MeSH$$aHIV Infections: virology
000282595 650_2 $$2MeSH$$aHIV Infections: metabolism
000282595 650_2 $$2MeSH$$ap21-Activated Kinases: metabolism
000282595 650_2 $$2MeSH$$aInterferon-Induced Helicase, IFIH1: metabolism
000282595 650_2 $$2MeSH$$aCD4-Positive T-Lymphocytes: immunology
000282595 650_2 $$2MeSH$$aCD4-Positive T-Lymphocytes: virology
000282595 650_2 $$2MeSH$$aHEK293 Cells
000282595 650_2 $$2MeSH$$aImmunity, Innate
000282595 650_2 $$2MeSH$$aDendritic Cells: immunology
000282595 650_2 $$2MeSH$$aPhosphorylation
000282595 650_2 $$2MeSH$$aMacrophages: immunology
000282595 650_2 $$2MeSH$$aMacrophages: virology
000282595 650_2 $$2MeSH$$aProtein Phosphatase 1: metabolism
000282595 650_2 $$2MeSH$$aInterferons: metabolism
000282595 650_2 $$2MeSH$$aInterferons: immunology
000282595 650_2 $$2MeSH$$aVirus Replication
000282595 7001_ $$aPrelli Bozzo, Caterina$$b1
000282595 7001_ $$aAcharya, Dhiraj$$b2
000282595 7001_ $$0P:(DE-2719)9003803$$aDe Luna, Aurora$$b3$$udzne
000282595 7001_ $$0P:(DE-2719)9003503$$aHirschenberger, Maximilian$$b4$$udzne
000282595 7001_ $$00000-0003-2968-180X$$aZhu, Junji$$b5
000282595 7001_ $$00000-0001-6406-7683$$aVolcic, Meta$$b6
000282595 7001_ $$aStolp, Bettina$$b7
000282595 7001_ $$aRodriguez-Quinteros, Cristina M$$b8
000282595 7001_ $$00000-0003-2982-4209$$aFackler, Oliver T$$b9
000282595 7001_ $$00000-0002-2163-2598$$aGack, Michaela U$$b10
000282595 7001_ $$0P:(DE-2719)9003481$$aSparrer, Konstantin M J$$b11
000282595 7001_ $$00000-0002-7052-2360$$aKirchhoff, Frank$$b12
000282595 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-025-67028-5$$gVol. 16, no. 1, p. 10945$$n1$$p10945$$tNature Communications$$v16$$x2041-1723$$y2025
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