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@ARTICLE{Lalibert:282595,
      author       = {Laliberté, Alexandre and Prelli Bozzo, Caterina and
                      Acharya, Dhiraj and De Luna, Aurora and Hirschenberger,
                      Maximilian and Zhu, Junji and Volcic, Meta and Stolp,
                      Bettina and Rodriguez-Quinteros, Cristina M and Fackler,
                      Oliver T and Gack, Michaela U and Sparrer, Konstantin M J
                      and Kirchhoff, Frank},
      title        = {{N}ef stabilizes actin to prevent {HIV}-1 sensing by
                      {RIG}-{I}-like receptors.},
      journal      = {Nature Communications},
      volume       = {16},
      number       = {1},
      issn         = {2041-1723},
      address      = {[London]},
      publisher    = {Springer Nature},
      reportid     = {DZNE-2025-01353},
      pages        = {10945},
      year         = {2025},
      abstract     = {Sensing 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.},
      keywords     = {Humans / HIV-1: immunology / HIV-1: genetics / nef Gene
                      Products, Human Immunodeficiency Virus: metabolism / nef
                      Gene Products, Human Immunodeficiency Virus: genetics / nef
                      Gene Products, Human Immunodeficiency Virus: immunology /
                      Actins: metabolism / Receptors, Immunologic / DEAD Box
                      Protein 58: metabolism / HIV Infections: immunology / HIV
                      Infections: virology / HIV Infections: metabolism /
                      p21-Activated Kinases: metabolism / Interferon-Induced
                      Helicase, IFIH1: metabolism / CD4-Positive T-Lymphocytes:
                      immunology / CD4-Positive T-Lymphocytes: virology / HEK293
                      Cells / Immunity, Innate / Dendritic Cells: immunology /
                      Phosphorylation / Macrophages: immunology / Macrophages:
                      virology / Protein Phosphatase 1: metabolism / Interferons:
                      metabolism / Interferons: immunology / Virus Replication /
                      nef Gene Products, Human Immunodeficiency Virus (NLM
                      Chemicals) / Actins (NLM Chemicals) / Receptors, Immunologic
                      (NLM Chemicals) / DEAD Box Protein 58 (NLM Chemicals) / nef
                      protein, Human immunodeficiency virus 1 (NLM Chemicals) /
                      p21-Activated Kinases (NLM Chemicals) / RIGI protein, human
                      (NLM Chemicals) / Interferon-Induced Helicase, IFIH1 (NLM
                      Chemicals) / PAK2 protein, human (NLM Chemicals) / IFIH1
                      protein, human (NLM Chemicals) / Protein Phosphatase 1 (NLM
                      Chemicals) / Interferons (NLM Chemicals)},
      cin          = {AG Sparrer},
      ddc          = {500},
      cid          = {I:(DE-2719)1910003},
      pnm          = {351 - Brain Function (POF4-351)},
      pid          = {G:(DE-HGF)POF4-351},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41354661},
      doi          = {10.1038/s41467-025-67028-5},
      url          = {https://pub.dzne.de/record/282595},
}