{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:43:48Z","timestamp":1789987428943,"version":"4.0.1"},"reference-count":35,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2017,2,21]],"date-time":"2017-02-21T00:00:00Z","timestamp":1487635200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,3,8]],"date-time":"2017-03-08T00:00:00Z","timestamp":1488931200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100000925","name":"Department of Health | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1033068"],"award-info":[{"award-number":["APP1033068"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"Department of Health | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1047252"],"award-info":[{"award-number":["APP1047252"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"Department of Health | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1059167"],"award-info":[{"award-number":["APP1059167"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005189","name":"Estonian Research Council","doi-asserted-by":"publisher","award":["20-27"],"award-info":[{"award-number":["20-27"]}],"id":[{"id":"10.13039\/501100005189","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2017,3,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Mosquito-transmitted chikungunya virus (CHIKV) is an arthritogenic alphavirus of the\n            <jats:italic>Togaviridae<\/jats:italic>\n            family responsible for frequent outbreaks of arthritic disease in humans. Capsid protein, a structural protein encoded by the CHIKV RNA genome, is able to translocate to the host cell nucleolus. In encephalitic alphaviruses, nuclear translocation induces host cell transcriptional shutoff; however, the role of capsid protein nucleolar localization in arthritogenic alphaviruses remains unclear. Using recombinant enhanced green fluorescent protein (EGFP)-tagged expression constructs and CHIKV infectious clones, we describe a nucleolar localization sequence (NoLS) in the N-terminal region of capsid protein, previously uncharacterized in CHIKV. Mutation of the NoLS by site-directed mutagenesis reduced efficiency of nuclear import of CHIKV capsid protein. In the virus, mutation of the capsid protein NoLS (CHIKV-NoLS) attenuated replication in mammalian and mosquito cells, producing a small-plaque phenotype. Attenuation of CHIKV-NoLS is likely due to disruption of the viral replication cycle downstream of viral RNA synthesis. In mice, CHIKV-NoLS infection caused no disease signs compared to wild-type CHIKV (CHIKV-WT)-infected mice; lack of disease signs correlated with significantly reduced viremia and decreased expression of proinflammatory factors. Mice immunized with CHIKV-NoLS, challenged with CHIKV-WT at 30\u00a0days postimmunization, develop no disease signs and no detectable viremia. Serum from CHIKV-NoLS-immunized mice is able to efficiently neutralize CHIKV infection\n            <jats:italic>in vitro<\/jats:italic>\n            . Additionally, CHIKV-NoLS-immunized mice challenged with the related alphavirus Ross River virus showed reduced early and peak viremia postchallenge, indicating a cross-protective effect. The high degree of CHIKV-NoLS attenuation may improve CHIKV antiviral and rational vaccine design.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            CHIKV is a mosquito-borne pathogen capable of causing explosive epidemics of incapacitating joint pain affecting millions of people. After a series of major outbreaks over the last 10\u00a0years, CHIKV and its mosquito vectors have been able to expand their range extensively, now making CHIKV a human pathogen of global importance. With no licensed vaccine or antiviral therapy for the treatment of CHIKV disease, there is a growing need to understand the molecular determinants of viral pathogenesis. These studies identify a previously uncharacterized nucleolar localization sequence (NoLS) in CHIKV capsid protein, begin a functional analysis of site-directed mutants of the capsid protein NoLS, and examine the effect of the NoLS mutation on CHIKV pathogenesis\n            <jats:italic>in vivo<\/jats:italic>\n            and its potential to influence CHIKV vaccine design. A better understanding of the pathobiology of CHIKV disease will aid the development of effective therapeutic strategies.\n          <\/jats:p>","DOI":"10.1128\/mbio.01970-16","type":"journal-article","created":{"date-parts":[[2017,2,22]],"date-time":"2017-02-22T01:10:23Z","timestamp":1487725823000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":50,"title":["Mutation of the N-Terminal Region of Chikungunya Virus Capsid Protein: Implications for Vaccine Design"],"prefix":"10.1128","volume":"8","author":[{"given":"Adam","family":"Taylor","sequence":"first","affiliation":[{"name":"Institute for Glycomics, Griffith University, Gold Coast Campus, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute for Glycomics, Griffith University, Gold Coast Campus, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Zaid","sequence":"additional","affiliation":[{"name":"Institute for Glycomics, Griffith University, Gold Coast Campus, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Y. 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