UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology; Thompson Lab

Publication Date

2021-06-23

Document Type

Article

Disciplines

Biochemistry, Biophysics, and Structural Biology | Immunology and Infectious Disease | Virology

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.

Keywords

Herpes virus, Post-translational modifications

Rights and Permissions

Copyright © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

DOI of Published Version

10.1038/s41467-021-24178-6

Source

Griffante G, Gugliesi F, Pasquero S, Dell'Oste V, Biolatti M, Salinger AJ, Mondal S, Thompson PR, Weerapana E, Lebbink RJ, Soppe JA, Stamminger T, Girault V, Pichlmair A, Oroszlán G, Coen DM, De Andrea M, Landolfo S. Human cytomegalovirus-induced host protein citrullination is crucial for viral replication. Nat Commun. 2021 Jun 23;12(1):3910. doi: 10.1038/s41467-021-24178-6. PMID: 34162877; PMCID: PMC8222335. Link to article on publisher's site

Journal/Book/Conference Title

Nature communications

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

34162877

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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