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Its genome contains multiple accessory protein genes that act against host immune responses but are not required for progeny virus production. The functions of the accessory proteins in the viral life cycle have been examined, but their involvement in viral pathogenicity remains unclear. Here, we investigated the roles of the accessory proteins in viral immunopathogenicity. To this end,\u00a0recombinant SARS\u2010CoV\u20102 possessing nonsense mutations in the seven accessory protein open reading frames (ORFs) (ORF3a, ORF3b, ORF6, ORF7a, ORF8, ORF9b, and ORF10)\u00a0was de novo generated using an early pandemic SARS\u2010CoV\u20102 strain as a backbone. We confirmed that the resultant virus (termed ORF3\u201310 KO) did not express accessory proteins in infected cells and retained the desired mutations in the viral genome. In cell culture, the ORF3\u201310 KO virus exhibited similar virus growth kinetics as the parental virus. In hamsters, ORF3\u201310 KO virus infection resulted in mild weight loss and reduced viral replication in the oral cavity and lung tissue. ORF3\u201310 KO virus infection led to mild inflammation, indicating that an inability to evade innate immune sensing because of a lack of accessory proteins impairs virus growth in vivo and results in quick elimination from the body. Overall, we showed that SARS\u2010CoV\u20102 accessory proteins are involved in immunopathogenicity.<\/jats:p>","DOI":"10.1111\/1348-0421.13157","type":"journal-article","created":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T09:03:48Z","timestamp":1717491828000},"page":"237-247","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Involvement of SARS\u2010CoV\u20102 accessory proteins in immunopathogenesis"],"prefix":"10.1111","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5748-3571","authenticated-orcid":false,"given":"Hayato","family":"Ito","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology Faculty of Medicine Hokkaido University Sapporo 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