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
Related Resources
PubMed ID
34162877
Repository Citation
Griffante G, Salinger AJ, Mondal S, Thompson PR, De Andrea M, Landolfo S. (2021). Human cytomegalovirus-induced host protein citrullination is crucial for viral replication. Open Access Publications by UMass Chan Authors. https://doi.org/10.1038/s41467-021-24178-6. Retrieved from https://escholarship.umassmed.edu/oapubs/4810
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Immunology and Infectious Disease Commons, Virology Commons
Comments
Full author list omitted for brevity. For the full list of authors, see article.