{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:49:28Z","timestamp":1790693368006,"version":"4.1.0"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2017,2,7]],"date-time":"2017-02-07T00:00:00Z","timestamp":1486425600000},"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\/100015311","name":"Novartis Institutes for Biomedical Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015311","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100011893","name":"Pan American Health Organization","doi-asserted-by":"crossref","award":["SCON2016-01353\/Brazil Ministry of Health"],"award-info":[{"award-number":["SCON2016-01353\/Brazil Ministry of Health"]}],"id":[{"id":"10.13039\/100011893","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI087856"],"award-info":[{"award-number":["R01AI087856"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007865","name":"University of Texas Medical Branch","doi-asserted-by":"publisher","award":["STARs Award"],"award-info":[{"award-number":["STARs Award"]}],"id":[{"id":"10.13039\/100007865","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            Compared with other flaviviruses, Zika virus (ZIKV) is uniquely associated with congenital diseases in pregnant women. One recent study reported that (i) ZIKV has higher thermostability than dengue virus (DENV [a flavivirus closely related to ZIKV]), which might contribute to the disease outcome; (ii) the higher thermostability of ZIKV could arise from an extended loop structure in domain III of the viral envelope (E) protein and an extra hydrogen-bond interaction between E molecules (V. A. Kostyuchenko, E. X. Y. Lim, S. Zhang, G. Fibriansah, T.-S. Ng, J. S. G. Ooi, J. Shi, and S.-M. Lok, Nature 533:425\u2013428, 2016,\n            <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/doi.org\/10.1038\/nature17994\">https:\/\/doi.org\/10.1038\/nature17994<\/jats:ext-link>\n            ). Here we report the functional analysis of the structural information in the context of complete ZIKV and DENV-2 virions. Swapping the prM-E genes between ZIKV and DENV-2 switched the thermostability of the chimeric viruses, identifying the prM-E proteins as the major determinants for virion thermostability. Shortening the extended loop of the E protein by 1\u00a0amino acid was lethal for ZIKV assembly\/release. Mutations (Q350I and T351V) that abolished the extra hydrogen-bond interaction between the E proteins did not reduce ZIKV thermostability, indicating that the extra interaction does not increase the thermostability. Interestingly, mutant T351V was attenuated in A129 mice defective in type I interferon receptors, even though the virus retained the wild-type thermostability. Furthermore, we found that a chimeric ZIKV with the DENV-2 prM-E and a chimeric DENV-2 with the ZIKV prM-E were highly attenuated in A129 mice; these chimeric viruses were highly immunogenic and protective against DENV-2 and ZIKV challenge, respectively. These results indicate the potential of these chimeric viruses for vaccine development.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Analysis of a recently observed high-resolution structure of ZIKV led to a hypothesis that its unusual stability may contribute to the associated, unique disease outcomes. Here we performed a functional analysis to demonstrate that viral prM-E genes are the main determinants for the high stability of ZIKV. The extra hydrogen-bond interaction (observed in the high-resolution structure) between ZIKV E proteins did not enhance virion stability, whereas the extended loop of E protein (CD loop in domain III) was essential for ZIKV assembly. More importantly, we found that a chimeric ZIKV with DENV-2 prM-E genes and a chimeric DENV-2 with ZIKV prM-E genes were highly attenuated in A129 mice. Mice immunized with these chimeric viruses generated robust neutralizing antibody responses and were fully protected from DENV-2 and ZIKV challenge, respectively, indicating that these chimeric viruses could be further developed as vaccine candidates.\n          <\/jats:p>","DOI":"10.1128\/mbio.02134-16","type":"journal-article","created":{"date-parts":[[2017,2,8]],"date-time":"2017-02-08T01:10:32Z","timestamp":1486516232000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":73,"title":["Understanding Zika Virus Stability and Developing a Chimeric Vaccine through Functional Analysis"],"prefix":"10.1128","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0918-016X","authenticated-orcid":false,"given":"Xuping","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujiao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"College of Animal Science and Technology, Southwest University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio E.","family":"Muruato","sequence":"additional","affiliation":[{"name":"Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Institute for Translational Science, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno T. D.","family":"Nunes","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Se\u00e7\u00e3o de Arbovirologia e Febres Hemorr\u00e1gicas, Instituto Evandro Chagas, Minist\u00e9rio da Sa\u00fade, Ananindeua, Par\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele B. A.","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Se\u00e7\u00e3o de Arbovirologia e Febres Hemorr\u00e1gicas, Instituto Evandro Chagas, Minist\u00e9rio da Sa\u00fade, Ananindeua, Par\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro F. C.","family":"Vasconcelos","sequence":"additional","affiliation":[{"name":"Se\u00e7\u00e3o de Arbovirologia e Febres Hemorr\u00e1gicas, Instituto Evandro Chagas, Minist\u00e9rio da Sa\u00fade, Ananindeua, Par\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott C.","family":"Weaver","sequence":"additional","affiliation":[{"name":"Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Institute for Translational Science, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannan L.","family":"Rossi","sequence":"additional","affiliation":[{"name":"Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Yong","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Institute for Translational Science, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Sealy Center for Structural Biology &amp; Molecular Biophysics, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Department of Pharmacology &amp; Toxicology, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(52)90042-4"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1602113"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.6b00030"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2101.140894"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2015.04.021"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.ES.2016.21.32.30314"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2016.03.010"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1705.101939"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1600651"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.ES2014.19.14.20761"},{"key":"e_1_3_2_12_2","first-page":"712","volume-title":"FlaviviridaeFields virology","author":"Lindenbach BD","year":"2013","unstructured":"Lindenbach BD Murray CL Thiel HJ Rice CM . 2013. 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Ian","family":"Lipkin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2017,3,8]]},"references-count":29,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,3,8]]}},"alternative-id":["10.1128\/mBio.02134-16"],"URL":"https:\/\/doi.org\/10.1128\/mbio.02134-16","relation":{},"ISSN":["2161-2129","2150-7511"],"issn-type":[{"value":"2161-2129","type":"print"},{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,8]]},"assertion":[{"value":"2016-11-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-01-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-02-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e02134-16"}}