SAMD9L acts as an antiviral factor against HIV-1 and primate lentiviruses by restricting viral and cellular translation.

Autor: Legrand A; Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, UCBL1, CNRS UMR 5308, ENS de Lyon, Université de Lyon, Lyon, France., Dahoui C; Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, UCBL1, CNRS UMR 5308, ENS de Lyon, Université de Lyon, Lyon, France., De La Myre Mory C; Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, UCBL1, CNRS UMR 5308, ENS de Lyon, Université de Lyon, Lyon, France., Noy K; Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, UCBL1, CNRS UMR 5308, ENS de Lyon, Université de Lyon, Lyon, France.; Unité de Biologie des Infections Virales Émergentes, Institut Pasteur, Lyon, Université Paris Cité, Paris, France., Guiguettaz L; Laboratoire de Biologie et Modélisation de la Cellule (LBMC), Université de Lyon, INSERM U1293, CNRS UMR 5239, ENS de Lyon, UCBL1, Lyon, France., Versapuech M; Université Paris Cité, CNRS, Inserm, Institut Cochin, INSERM, CNRS, Paris, France., Loyer C; Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, UCBL1, CNRS UMR 5308, ENS de Lyon, Université de Lyon, Lyon, France., Pillon M; Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, UCBL1, CNRS UMR 5308, ENS de Lyon, Université de Lyon, Lyon, France., Wcislo M; Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, UCBL1, CNRS UMR 5308, ENS de Lyon, Université de Lyon, Lyon, France., Guéguen L; Laboratoire de Biologie et Biométrie Évolutive (LBBE), CNRS UMR 5558, UCBL1, Villeurbanne, France., Berlioz-Torrent C; Université Paris Cité, CNRS, Inserm, Institut Cochin, INSERM, CNRS, Paris, France., Cimarelli A; Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, UCBL1, CNRS UMR 5308, ENS de Lyon, Université de Lyon, Lyon, France., Mateo M; Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, UCBL1, CNRS UMR 5308, ENS de Lyon, Université de Lyon, Lyon, France.; Unité de Biologie des Infections Virales Émergentes, Institut Pasteur, Lyon, Université Paris Cité, Paris, France., Fiorini F; Retroviruses and structural biochemistry, Molecular Microbiology and Structural Biochemistry (MMSB), IBCP, CNRS UMR 5086, University of Lyon, Lyon, France., Ricci EP; Laboratoire de Biologie et Modélisation de la Cellule (LBMC), Université de Lyon, INSERM U1293, CNRS UMR 5239, ENS de Lyon, UCBL1, Lyon, France., Etienne L; Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, UCBL1, CNRS UMR 5308, ENS de Lyon, Université de Lyon, Lyon, France.
Jazyk: angličtina
Zdroj: PLoS biology [PLoS Biol] 2024 Jul 03; Vol. 22 (7), pp. e3002696. Date of Electronic Publication: 2024 Jul 03 (Print Publication: 2024).
DOI: 10.1371/journal.pbio.3002696
Abstrakt: Sterile alpha motif domain-containing proteins 9 and 9-like (SAMD9/9L) are associated with life-threatening genetic diseases in humans and are restriction factors of poxviruses. Yet, their cellular function and the extent of their antiviral role are poorly known. Here, we found that interferon-stimulated human SAMD9L restricts HIV-1 in the late phases of replication, at the posttranscriptional and prematuration steps, impacting viral translation and, possibly, endosomal trafficking. Surprisingly, the paralog SAMD9 exerted an opposite effect, enhancing HIV-1. More broadly, we showed that SAMD9L restricts primate lentiviruses, but not a gammaretrovirus (MLV), nor 2 RNA viruses (arenavirus MOPV and rhabdovirus VSV). Using structural modeling and mutagenesis of SAMD9L, we identified a conserved Schlafen-like active site necessary for HIV-1 restriction by human and a rodent SAMD9L. By testing a gain-of-function constitutively active variant from patients with SAMD9L-associated autoinflammatory disease, we determined that SAMD9L pathogenic functions also depend on the Schlafen-like active site. Finally, we found that the constitutively active SAMD9L strongly inhibited HIV, MLV, and, to a lesser extent, MOPV. This suggests that the virus-specific effect of SAMD9L may involve its differential activation/sensing and the virus ability to evade from SAMD9L restriction. Overall, our study identifies SAMD9L as an HIV-1 antiviral factor from the cell autonomous immunity and deciphers host determinants underlying the translational repression. This provides novel links and therapeutic avenues against viral infections and genetic diseases.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Legrand et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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