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The molecular mechanism of ZIKV virion assembly is largely unknown. Here, we report that ZIKV NS2A plays a central role in recruiting viral RNA, structural protein prM\/E, and viral NS2B\/NS3 protease to the virion assembly site and orchestrating virion morphogenesis. One mutation that impairs these interactions does not significantly affect viral RNA replication but selectively abolishes virion assembly, demonstrating the specific role of these interactions in virus morphogenesis. We also show that the 3\u02b9 UTR of ZIKV RNA may serve as a \u201crecruitment signal\u201d through binding to NS2A to enter the virion assembly site. Following a coordinated cleavage of C-prM-E at the virion assembly site, NS2A may present the viral RNA to C protein for nucleocapsid formation followed by envelopment with prM\/E proteins. The results have provided new insights into flavivirus virion assembly.<\/jats:p>","DOI":"10.1128\/mbio.02375-19","type":"journal-article","created":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T07:15:09Z","timestamp":1572333309000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":88,"title":["Zika Virus NS2A-Mediated Virion Assembly"],"prefix":"10.1128","volume":"10","author":[{"given":"Xianwen","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Biochemistry &amp; Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People\u2019s Republic of China"},{"name":"University of Chinese Academy of Sciences, Beijing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0918-016X","authenticated-orcid":false,"given":"Xuping","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjie","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linfen","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vsevolod L.","family":"Popov","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Institute for Human Infections &amp; Immunity, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinwen","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People\u2019s Republic of China"},{"name":"University of Chinese Academy of Sciences, Beijing, People\u2019s Republic of China"},{"name":"Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Yong","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Institute for Human Infections &amp; Immunity, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Sealy Institute for Vaccine Sciences, 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_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(02)00660-8"},{"key":"e_1_3_3_3_2","first-page":"747","volume-title":"Fields virology","author":"Pierson TC","year":"2013","unstructured":"Pierson TC, Diamond MS. 2013. 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