Antiviral intrinsic immunity - targeting old foes and new enemies | Institut Cochin

Antiviral intrinsic immunity - targeting old foes and new enemies

Thomas Gramberg (Institute of Clinical and Molecular Virology, Friedrich-Alexander University, Erlangen, Germany)

22 juin 2023

Séminaire

Infos pratiques

12h00 - 13h00

Salle Rosalind Franklin

Professionnel de recherche

Accès mobilité réduite

Methylation of the mRNA 5’ cap by methyltransferases enables efficient translation and avoids recognition by innate immune factors. We analyze SARS-CoV-2 lacking its 2’-O-methyltransferases Nsp16. We identified a dual role for the 2’-O-methyltransferase Nsp16 during SARS–CoV-2 replication in avoiding efficient recognition by the RNA sensor MDA5 and in shielding its RNA from interferon-induced antiviral responses, thereby identifying Nsp16 as potential candidate for therapeutic intervention.
Mobile genetic elements have significantly shaped our genomic landscape. LINE-1 retroelements are the only autonomously active elements left in the human genome and new insertions can have detrimental consequences. We demonstrate that the antiviral restriction factor TRIM5α senses and blocks LINE-1 retroelements.

Thomas Gramberg is invited by Florence Margottin-Goguet.

Selected publications

A frequent SNP in TRIM5α strongly enhances the innate immune response against LINE-1 elements. Lagisquet J, Conrad M, Wittmann S, Volkmann B, Weissinger H, Sticht H, Gramberg T.Front Immunol. 2023 Apr 26;14:1168589.

Nsp16 shields SARS-CoV-2 from efficient MDA5 sensing and IFIT1-mediated restriction. Russ A, Wittmann S, Tsukamoto Y, Herrmann A, Deutschmann J, Lagisquet J, Ensser A, Kato H, Gramberg T.EMBO Rep. 2022 Dec 6;23(12):e55648.

SAMHD1 … and Viral Ways around It. Deutschmann J, Gramberg T.Viruses. 2021 Mar 2;13(3):395.

Recognize Yourself-Innate Sensing of Non-LTR Retrotransposons. Lagisquet J, Zuber K, Gramberg T.Viruses. 2021 Jan 12;13(1):94. doi: 10.3390/v13010094.

Human TRIM5α senses and restricts LINE-1 elements. Volkmann B, Wittmann S, Lagisquet J, Deutschmann J, Eissmann K, Ross JJ, Biesinger B, Gramberg T. Proc Natl Acad Sci U S A. 2020 Jul 28;117(30):17965-17976.

A viral kinase counteracts in vivo restriction of murine cytomegalovirus by SAMHD1. Deutschmann J, Schneider A, Gruska I, Vetter B, Thomas D, Kießling M, Wittmann S, Herrmann A, Schindler M, Milbradt J, Ferreirós N, Winkler TH, Wiebusch L, Gramberg T. Nat Microbiol. 2019 Dec;4(12):2273-2284.

Human cytomegalovirus overcomes SAMHD1 restriction in macrophages via pUL97. Businger R, Deutschmann J, Gruska I, Milbradt J, Wiebusch L, Gramberg T, Schindler M. Nat Microbiol. 2019 Dec;4(12):2260-2272.

The SAMHD1-mediated block of LINE-1 retroelements is regulated by phosphorylation. Herrmann A, Wittmann S, Thomas D, Shepard CN, Kim B, Ferreirós N, Gramberg T. Mob DNA. 2018 Mar 28;9:11.

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