Human cytomegalovirus-induced host protein citrullination is crucial for viral replication

Gloria Griffante, Francesca Gugliesi, Selina Pasquero, Valentina Dell’Oste, Matteo Biolatti, Ari J. Salinger, Santanu Mondal, Paul R. Thompson, Eranthie Weerapana, Robert J. Lebbink, Jasper A. Soppe, Thomas Stamminger, Virginie Girault, Andreas Pichlmair, Gábor Oroszlán, Donald M. Coen, Marco De Andrea, Santo Landolfo

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Citrullination is the conversion of arginine-to-citrulline by protein arginine deiminases (PADs), whose dysregulation is implicated in the pathogenesis of various types of cancers and autoimmune diseases. Consistent with the ability of human cytomegalovirus (HCMV) to induce post-translational modifications of cellular proteins to gain a survival advantage, we show that HCMV infection of primary human fibroblasts triggers PAD-mediated citrullination of several host proteins, and that this activity promotes viral fitness. Citrullinome analysis reveals significant changes in deimination levels of both cellular and viral proteins, with interferon (IFN)-inducible protein IFIT1 being among the most heavily deiminated one. As genetic depletion of IFIT1 strongly enhances HCMV growth, and in vitro IFIT1 citrullination impairs its ability to bind to 5’-ppp-RNA, we propose that viral-induced IFIT1 citrullination is a mechanism of HCMV evasion from host antiviral resistance. Overall, our findings point to a crucial role of citrullination in subverting cellular responses to viral infection.

Original languageEnglish
Article number3910
JournalNature Communications
Volume12
Issue number1
DOIs
StatePublished - 1 Dec 2021
Externally publishedYes

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