{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T18:07:55Z","timestamp":1783966075957,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014426","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000}}],"reference-count":75,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32202886"],"award-info":[{"award-number":["32202886"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20220576"],"award-info":[{"award-number":["BK20220576"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Cangzhou city, Hebei Province, China","award":["23241002009N"],"award-info":[{"award-number":["23241002009N"]}]},{"name":"Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses"},{"name":"Innovation and Entrepreneurship Team of Jiangsu Province","award":["JSSCTD202224"],"award-info":[{"award-number":["JSSCTD202224"]}]},{"name":"the 111 Project","award":["D18007"],"award-info":[{"award-number":["D18007"]}]},{"DOI":"10.13039\/501100012246","name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Mosquito-borne orthoflavivirus, such as Japanese encephalitis virus (JEV), Dengue virus (DENV), and Zika virus (ZIKV), pose a serious global health threat. As obligate intracellular parasites, they often hijack the host ubiquitin system to modify their own proteins, thereby regulating the viral life cycle, host adaptation, transmission, and pathogenesis. Despite its critical roles, the precise molecular mechanisms and functional significance of viral protein ubiquitination in orthoflavivirus infection remain incompletely understood. Here, we identify JEV prM as a novel target for host-specific ubiquitination, which occurs exclusively in vertebrate hosts but not in mosquitoes. Ubiquitin conjugation at the evolutionarily conserved lysine residues (K107\/108\/116) in multiple mosquito-borne orthoflaviviruses (USUV, MVEV, and WNV) confers differential adaptation between vertebrate hosts and mosquito vectors. Mechanistically, prM ubiquitination serves as a recruitment signal for the ESCRT-I subunit TSG101, an early-acting component of the ESCRT machinery, which in turn serves as an adaptor to recruit downstream ESCRT components (VPS28, CHMP2A, and CHMP4B), thereby driving viral particle budding. These findings elucidate a novel mechanism by which viral protein ubiquitination regulates JEV infection and host adaptation, and provide important insights into the adaptive evolution of orthoflaviviruses across different hosts and vectors.<\/jats:p>","DOI":"10.1371\/journal.ppat.1014426","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T17:44:17Z","timestamp":1783532657000},"page":"e1014426","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Host-specific ubiquitination of prM orchestrates ESCRT recruitment to mediate efficient Japanese Encephalitis Virus assembly in vertebrates"],"prefix":"10.1371","volume":"22","author":[{"given":"Chenxi","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhuang","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linjie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyang","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2141-5139","authenticated-orcid":true,"given":"Yanhua","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"issue":"1","key":"ppat.1014426.ref001","doi-asserted-by":"crossref","first-page":"2814","DOI":"10.1080\/21505594.2021.1996059","article-title":"Pathogenesis 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