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Currently, there is no specific treatment or vaccine available, and more effort is needed to identify cellular factors in the viral life cycle. Here, we investigated interactors of ZIKV envelope (E) protein by combining protein pull-down with mass spectrometry. We found that E interacts with the endoplasmic reticulum (ER) resident chaperone, glucose regulated protein 78 (GRP78). Although other flaviviruses are known to co-opt ER resident proteins, including GRP78, to enhance viral infectivity, the role ER proteins play during the ZIKV life cycle is yet to be elucidated. We showed that GRP78 levels increased during ZIKV infection and localised to sites coincident with ZIKV E staining. Depletion of GRP78 using specific siRNAs significantly reduced reporter-virus luciferase readings, viral protein synthesis, and viral titres. Additionally, GRP78 depletion reduced the ability of ZIKV to disrupt host cell translation and altered the localisation of viral replication factories, though there was no effect on viral RNA synthesis. In summary, we showed GRP78 is a vital host-factor during ZIKV infection, which may be involved in the coordination of viral replication factories.<\/jats:p>","DOI":"10.3390\/v12050524","type":"journal-article","created":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T10:01:18Z","timestamp":1589191278000},"page":"524","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Glucose-Regulated Protein 78 Interacts with Zika Virus Envelope Protein and Contributes to a Productive Infection"],"prefix":"10.3390","volume":"12","author":[{"given":"Jamie","family":"Royle","sequence":"first","affiliation":[{"name":"MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Ram\u00edrez-Santana","sequence":"additional","affiliation":[{"name":"Center for Autoimmune Diseases Research-CREA, School of Medicine and Health Sciences, Universidad del Rosario, 110010 Bogot\u00e1, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Snezhana","family":"Akpunarlieva","sequence":"additional","affiliation":[{"name":"Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4370-0707","authenticated-orcid":false,"given":"Claire L.","family":"Donald","sequence":"additional","affiliation":[{"name":"MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4609-3551","authenticated-orcid":false,"given":"Rommel J.","family":"Gestuveo","sequence":"additional","affiliation":[{"name":"MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK"},{"name":"Division of Biological Sciences, College of Arts and Sciences, University of the Philippines Visayas, 5023 Miagao, Iloilo, Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan-Manuel","family":"Anaya","sequence":"additional","affiliation":[{"name":"Center for Autoimmune Diseases Research-CREA, School of Medicine and Health Sciences, Universidad del Rosario, 110010 Bogot\u00e1, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres","family":"Merits","sequence":"additional","affiliation":[{"name":"Institute of Technology, University of Tartu, 50411 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1663-9004","authenticated-orcid":false,"given":"Richard","family":"Burchmore","sequence":"additional","affiliation":[{"name":"Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Kohl","sequence":"additional","affiliation":[{"name":"MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2608-5148","authenticated-orcid":false,"given":"Margus","family":"Varjak","sequence":"additional","affiliation":[{"name":"MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/0035-9203(64)90201-9","article-title":"Zika Virus Infection in Man","volume":"58","author":"Simpson","year":"1964","journal-title":"Trans. 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