Amino acid substitutions in norovirus VP1 dictate host dissemination via variations in cellular attachment.

Autor:	Mills JT; Astbury Centre for Structural Molecular Biology, School of Molecular & Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom., Minogue SC; Astbury Centre for Structural Molecular Biology, School of Molecular & Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom., Snowden JS; Astbury Centre for Structural Molecular Biology, School of Molecular & Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom., Arden WKC; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA., Rowlands DJ; Astbury Centre for Structural Molecular Biology, School of Molecular & Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom., Stonehouse NJ; Astbury Centre for Structural Molecular Biology, School of Molecular & Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom., Wobus CE; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA., Herod MR; Astbury Centre for Structural Molecular Biology, School of Molecular & Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.
Jazyk:	angličtina
Zdroj:	Journal of virology [J Virol] 2023 Dec 21; Vol. 97 (12), pp. e0171923. Date of Electronic Publication: 2023 Nov 30.
DOI:	10.1128/jvi.01719-23
Abstrakt:	Importance: All viruses initiate infection by utilizing receptors to attach to target host cells. These virus-receptor interactions can therefore dictate viral replication and pathogenesis. Understanding the nature of virus-receptor interactions could also be important for the development of novel therapies. Noroviruses are non-enveloped icosahedral viruses of medical importance. They are a common cause of acute gastroenteritis with no approved vaccine or therapy and are a tractable model for studying fundamental virus biology. In this study, we utilized the murine norovirus model system to show that variation in a single amino acid of the major capsid protein alone can affect viral infectivity through improved attachment to suspension cells. Modulating plasma membrane mobility reduced infectivity, suggesting an importance of membrane mobility for receptor recruitment and/or receptor conformation. Furthermore, different substitutions at this site altered viral tissue distribution in a murine model, illustrating how in-host capsid evolution could influence viral infectivity and/or immune evasion. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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