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Simultaneous membrane and RNA binding by tick-borne encephalitis virus capsid protein
Faculty of Biological and Environmental Sciences, Molecular and Integrative Bioscience Research Programme, University of Helsinki, Helsinki, Finland; University of Helsinki, Helsinki Institute of Life Sciences-Institute of Biotechnology, Helsinki, Finland.
Faculty of Biological and Environmental Sciences, Molecular and Integrative Bioscience Research Programme, University of Helsinki, Helsinki, Finland; University of Helsinki, Helsinki Institute of Life Sciences-Institute of Biotechnology, Helsinki, Finland.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).ORCID iD: 0000-0001-5116-2577
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2023 (English)In: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 19, no 2, article id e1011125Article in journal (Refereed) Published
Abstract [en]

Tick-borne encephalitis virus is an enveloped, pathogenic, RNA virus in the family Flaviviridae, genus Flavivirus. Viral particles are formed when the nucleocapsid, consisting of an RNA genome and multiple copies of the capsid protein, buds through the endoplasmic reticulum membrane and acquires the viral envelope and the associated proteins. The coordination of the nucleocapsid components to the sites of assembly and budding are poorly understood. Here, we investigate the interactions of the wild-type and truncated capsid proteins with membranes with biophysical methods and model membrane systems. We show that capsid protein initially binds membranes via electrostatic interactions with negatively-charged lipids, which is followed by membrane insertion. Additionally, we show that membrane-bound capsid protein can recruit viral genomic RNA. We confirm the biological relevance of the biophysical findings by using mass spectrometry to show that purified virions contain negatively-charged lipids. Our results suggest that nucleocapsid assembly is coordinated by negatively-charged membrane patches on the endoplasmic reticulum and that the capsid protein mediates direct contacts between the nucleocapsid and the membrane.

Place, publisher, year, edition, pages
Public Library of Science , 2023. Vol. 19, no 2, article id e1011125
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Microbiology in the medical area
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URN: urn:nbn:se:umu:diva-205497DOI: 10.1371/journal.ppat.1011125ISI: 000966733300001PubMedID: 36787339Scopus ID: 2-s2.0-85149054055OAI: oai:DiVA.org:umu-205497DiVA, id: diva2:1743206
Available from: 2023-03-14 Created: 2023-03-14 Last updated: 2023-09-05Bibliographically approved

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Lindgren, MariePace, HudsonÖverby, Anna K.Bally, MartaLundmark, Richard

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Lindgren, MariePace, HudsonÖverby, Anna K.Bally, MartaLundmark, Richard
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Department of Clinical MicrobiologyMolecular Infection Medicine Sweden (MIMS)Wallenberg Centre for Molecular Medicine at Umeå University (WCMM)Department of Integrative Medical Biology (IMB)
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