{"data":{"id":"10.6084/m9.figshare.24925288","type":"dois","attributes":{"doi":"10.6084/m9.figshare.24925288","prefix":"10.6084","suffix":"m9.figshare.24925288","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Landers, V Douglas","givenName":"V Douglas","familyName":"Landers","affiliation":[],"nameIdentifiers":[]},{"name":"Thomas, Milton","givenName":"Milton","familyName":"Thomas","affiliation":[],"nameIdentifiers":[]},{"name":"Isom, Cierra M.","givenName":"Cierra M.","familyName":"Isom","affiliation":[],"nameIdentifiers":[]},{"name":"Karki, Deepa","givenName":"Deepa","familyName":"Karki","affiliation":[],"nameIdentifiers":[]},{"name":"Sokoloski, Kevin J.","givenName":"Kevin J.","familyName":"Sokoloski","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"Capsid protein mediated evasion of IRAK1-dependent signalling is essential to Sindbis virus neuroinvasion and virulence in mice"}],"publisher":"Taylor \u0026 Francis","container":{},"publicationYear":2024,"subjects":[{"subject":"Biochemistry"},{"subject":"Medicine"},{"subject":"Microbiology"},{"subject":"FOS: Biological sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Molecular Biology"},{"subject":"Evolutionary Biology"},{"subject":"Environmental Sciences not elsewhere classified"},{"subject":"Ecology"},{"subject":"Immunology"},{"subject":"FOS: Clinical medicine","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Mental Health"},{"subject":"Infectious Diseases"},{"subject":"FOS: Health sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Plant Biology"},{"subject":"Virology"}],"contributors":[],"dates":[{"date":"2024-01-07","dateType":"Created"},{"date":"2024-12-07","dateType":"Updated"},{"date":"2024","dateType":"Issued"}],"language":null,"types":{"ris":"DATA","bibtex":"misc","citeproc":"dataset","schemaOrg":"Dataset","resourceType":"Dataset","resourceTypeGeneral":"Dataset"},"relatedIdentifiers":[{"relationType":"IsSupplementTo","relatedIdentifier":"10.1080/22221751.2023.2300452","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":["24560043 Bytes"],"formats":[],"version":null,"rightsList":[{"rights":"Creative Commons Attribution 4.0 International","rightsUri":"https://creativecommons.org/licenses/by/4.0/legalcode","schemeUri":"https://spdx.org/licenses/","rightsIdentifier":"cc-by-4.0","rightsIdentifierScheme":"SPDX"}],"descriptions":[{"description":"Alphaviruses are arthropod-borne, single-stranded positive-sense RNA viruses that are recognized as rapidly emerging pathogens. Despite being exquisitely sensitive to the effects of the innate immune response alphaviruses can readily replicate, disseminate, and induce pathogenesis in immunologically competent hosts. Nonetheless, how alphaviruses evade the induction of an innate immune response prior to viral gene expression, or in non-permissive infections, is unknown. Previously we reported the identification of a novel host/pathogen interaction between the viral Capsid (CP) protein and the host IRAK1 protein. The CP/IRAK1 interaction was determined to negatively impact IRAK1-dependent PAMP detection \u003ci\u003ein vitro\u003c/i\u003e, however, the precise importance of the CP/IRAK1 interaction to alphaviral infection remained unknown. Here we detail the identification of the CP/IRAK1 interaction determinants of the Sindbis virus (SINV) CP protein and examine the importance of the interaction to alphaviral infection and pathogenesis \u003ci\u003ein vivo\u003c/i\u003e using an interaction deficient mutant of the model neurotropic strain of SINV. Importantly, these interaction determinants are highly conserved across multiple Old-World alphaviruses, including Ross River virus (RRV), Mayaro virus (MAYV), Chikungunya virus (CHIKV), and Semliki Forest virus (SFV). In the absence of a functional CP/IRAK1 interaction, SINV replication is significantly restricted and fails to disseminate from the primary site of inoculation due to the induction of a robust type-I Interferon response. Altogether these data indicate that the evasion of IRAK1-dependent signalling is critical to overcoming the host innate immune response and the \u003ci\u003ein vivo\u003c/i\u003e data presented here demonstrate the importance of the CP/IRAK1 interaction to neurovirulence and pathogenesis.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"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