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Here, CHIKVs with mutations in non\u2010structural proteins (nsPs) were investigated for their suitability as attenuated CHIKV vaccines. R532H mutation in nsP1 caused reduced infectivity in mouse tail fibroblasts but an enhanced type\u2010I IFN response compared to WT\u2010CHIKV. Adult mice infected with this nsP\u2010mutant exhibited a mild joint phenotype with low\u2010level viremia that rapidly cleared. Mechanistically, ingenuity pathway analyses revealed a tilt in the anti\u2010inflammatory IL\u201010 versus pro\u2010inflammatory IL\u20101\u03b2 and IL\u201018 balance during CHIKV nsP\u2010mutant infection that modified acute antiviral and cell signaling canonical pathways. Challenging CHIKV nsP\u2010mutant\u2010infected mice with WT\u2010CHIKV or the closely related O'nyong\u2010nyong virus resulted in no detectable viremia, observable joint inflammation, or damage. Challenged mice showed high antibody titers with efficient neutralizing capacity, indicative of immunological memory. Manipulating molecular processes that govern CHIKV replication could lead to plausible vaccine candidates against alphavirus infection.<\/jats:p>","DOI":"10.15252\/emmm.201810092","type":"journal-article","created":{"date-parts":[[2019,4,23]],"date-time":"2019-04-23T11:02:14Z","timestamp":1556017334000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Mutating chikungunya virus non\u2010structural protein produces potent live\u2010attenuated vaccine candidate"],"prefix":"10.1038","volume":"11","author":[{"given":"Yi\u2010Hao","family":"Chan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teck\u2010Hui","family":"Teo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Age","family":"Utt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeslin JL","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siti Naqiah","family":"Amrun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhana","family":"Abu Bakar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wearn\u2010Xin","family":"Yee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Becht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl Yi\u2010Pin","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernett","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravisankar","family":"Rajarethinam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Newell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres","family":"Merits","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Carissimo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5645-7048","authenticated-orcid":false,"given":"Fok\u2010Moon","family":"Lum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4071-5222","authenticated-orcid":false,"given":"Lisa FP","family":"Ng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,4,23]]},"reference":[{"key":"BFEMMM201810092_CR1","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/nbt.2594","volume":"31","author":"EAD Amir","year":"2013","unstructured":"Amir EAD, Davis KL, Tadmor MD, Simonds EF, Levine JH, Bendall SC, Shenfeld DK, Krishnaswamy S, Nolan GP, Pe'Er D (2013) ViSNE enables visualization of high dimensional single\u2010cell data and reveals phenotypic heterogeneity of leukemia. 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