Sun, K., Appadoo, F., Liu, Y. et al. (4 more authors) (2024) A novel interaction between the 5′ untranslated region of the Chikungunya virus genome and Musashi RNA binding protein is essential for efficient virus genome replication. Nucleic Acids Research, 52 (17). pp. 10654-10667. ISSN 0305-1048
Abstract
Chikungunya virus (CHIKV) is a re-emerging, pathogenic alphavirus that is transmitted to humans by Aedesspp. mosquitoes—causing fever and debilitating joint pain, with frequent long-term health implications and high morbidity. The CHIKV replication cycle is poorly understood and specific antiviral therapeutics are lacking. In the current study, we identify host cell Musashi RNA binding protein-2 (MSI-2) as a proviral factor. MSI-2 depletion and small molecule inhibition assays demonstrated that MSI-2 is required for efficient CHIKV genome replication. Depletion of both MSI-2 and MSI-1 homologues was found to synergistically inhibit CHIKV replication, suggesting redundancy in their proviral function. Electromobility shift assay (EMSA) competition studies demonstrated that MSI-2 interacts specifically with an RNA binding motif within the 5′ untranslated region (5′UTR) of CHIKV and reverse genetic analysis showed that mutation of the binding motif inhibited genome replication and blocked rescue of mutant virus. For the first time, this study identifies the proviral role of MSI RNA binding proteins in the replication of the CHIKV genome, providing important new insight into mechanisms controlling replication of this significant human pathogen and the potential of a novel therapeutic target.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2024. This is an open access article under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Funding Information: | Funder Grant number MRC (Medical Research Council) MR/N01054X/1 |
Depositing User: | Symplectic Publications |
Date Deposited: | 04 Jul 2024 10:35 |
Last Modified: | 30 Sep 2024 12:56 |
Status: | Published |
Publisher: | Oxford University Press |
Identification Number: | 10.1093/nar/gkae619 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:214408 |