{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T04:51:26Z","timestamp":1776142286864,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T00:00:00Z","timestamp":1775952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"crossref","award":["2025ZD01900706"],"award-info":[{"award-number":["2025ZD01900706"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Science and Technology Leading Talent Program of Yunnan Province","award":["202405AB350002"],"award-info":[{"award-number":["202405AB350002"]}]},{"name":"High-Level Medical Talent Training Program of Yunnan Province","award":["L-2024018"],"award-info":[{"award-number":["L-2024018"]}]},{"name":"Major Basic Research Projects of Yunnan Science and Technology Department","award":["202401BC070008"],"award-info":[{"award-number":["202401BC070008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Chikungunya virus (CHIKV) pathogenesis research has long been constrained by the lack of suitable immunocompetent rodent models. Through serial passaging in A129 and C57BL\/6 mice, we obtained an adapted strain (CHIKV-Adapt) harboring an E2-K200R substitution along with non-structural protein mutations. Phenotypic analysis in C57BL\/6 mice, BALB\/c mice, and hamster models demonstrated that compared to the wild-type virus CHIKV-Adapt induced significantly higher and more prolonged viremia, broader tissue tropism, and more severe internal joint inflammation, without exacerbating external swelling. Notably, the K200R mutation did not alter the viral replication kinetics in vitro and was predicted not to affect its binding pattern to the MXRA8 receptor. Furthermore, mice challenged 160 days after primary infection exhibited nearly complete protective immunity. These findings indicate that E2-K200R is a critical adaptive mutation that, together with accompanying non-structural mutations, significantly enhances CHIKV replication capacity and pathogenicity in immunocompetent rodents without changing its in vitro replication ability or predicted receptor-binding mode. The acquisition of this adapted strain provides a new tool for CHIKV pathogenesis research and vaccine evaluation.<\/jats:p>","DOI":"10.3390\/v18040459","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T10:19:14Z","timestamp":1776075554000},"page":"459","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Mouse-Adapted CHIKV Strain Harboring E2-K200R and Non-Structural Mutations Exhibits Enhanced Pathogenicity in Multiple Rodent Models"],"prefix":"10.3390","volume":"18","author":[{"given":"Cong","family":"Tang","sequence":"first","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College (IMBCAMS&PUMC), 935 Jiaoling Road, Kunming 650118, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bai","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College (IMBCAMS&PUMC), 935 Jiaoling Road, Kunming 650118, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6390-9604","authenticated-orcid":false,"given":"Qing","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College (IMBCAMS&PUMC), 935 Jiaoling Road, Kunming 650118, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College (IMBCAMS&PUMC), 935 Jiaoling Road, Kunming 650118, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenhai","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College (IMBCAMS&PUMC), 935 Jiaoling Road, Kunming 650118, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College (IMBCAMS&PUMC), 935 Jiaoling Road, Kunming 650118, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daoju","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College (IMBCAMS&PUMC), 935 Jiaoling Road, Kunming 650118, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3662-6042","authenticated-orcid":false,"given":"Hao","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College (IMBCAMS&PUMC), 935 Jiaoling Road, Kunming 650118, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haixuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College (IMBCAMS&PUMC), 935 Jiaoling Road, Kunming 650118, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junbin","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College (IMBCAMS&PUMC), 935 Jiaoling Road, Kunming 650118, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1675-9735","authenticated-orcid":false,"given":"Shuaiyao","family":"Lu","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College (IMBCAMS&PUMC), 935 Jiaoling Road, Kunming 650118, China"},{"name":"Yunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, China"},{"name":"State Key Laboratory of Respiratory Health and Multimorbidity, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"},{"name":"Key Laboratory of Pathogen Infection Prevention and Control (Peking Union Medical College), Ministry of Education, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"},{"name":"Yunnan Provincial Key Laboratory of Vector-borne Diseases Control and Research, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/s41572-023-00429-2","article-title":"Chikungunya Fever","volume":"9","author":"Bartholomeeusen","year":"2023","journal-title":"Nat. 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