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However, it is unclear how the interplay between cross-reactive antibodies and T cells tilts the balance toward pathogenesis versus protection during secondary Zika virus (ZIKV) and Japanese encephalitis virus (JEV) infections. We show that sera and IgG from JEV-vaccinated humans and JEV-inoculated mice cross-reacted with ZIKV, exacerbated lethal ZIKV infection upon transfer to mice, and promoted viral replication and mortality upon ZIKV infection of the neonates born to immune mothers. In contrast, transfer of CD8+ T cells from JEV-exposed mice was protective, reducing the viral burden and mortality of ZIKV-infected mice and abrogating the lethal effects of antibody-mediated enhancement of ZIKV infection in mice. Conversely, cross-reactive anti-ZIKV antibodies or CD8+ T cells displayed the same pathogenic or protective effects upon JEV infection, with the exception that maternally acquired anti-ZIKV antibodies had no effect on JEV infection of the neonates. These results provide clues for developing safe anti-JEV\/ZIKV vaccines.<\/jats:p>","DOI":"10.1084\/jem.20192152","type":"journal-article","created":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T08:56:40Z","timestamp":1594889800000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["Japanese encephalitis virus\u2013primed CD8+ T cells prevent antibody-dependent enhancement of Zika virus pathogenesis"],"prefix":"10.1084","volume":"217","author":[{"given":"Dong","family":"Chen","sequence":"first","affiliation":[{"name":"Immunology Innovation Team, School of Medicine, Ningbo University, Ningbo, China 1"},{"name":"The Sixth People\u2019s Hospital of Wenzhou, Wenzhou, China 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiliang","family":"Duan","sequence":"additional","affiliation":[{"name":"Immunology Innovation Team, School of Medicine, Ningbo University, Ningbo, China 1"},{"name":"Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhua","family":"Zhou","sequence":"additional","affiliation":[{"name":"Immunology Innovation Team, School of Medicine, Ningbo University, Ningbo, China 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Zou","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengwei","family":"Jin","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital and Yuying Children\u2019s Hospital of Wenzhou Medical University, Wenzhou, China 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dezhou","family":"Li","sequence":"additional","affiliation":[{"name":"Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Chen","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital and Yuying Children\u2019s Hospital of Wenzhou Medical University, Wenzhou, China 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongchao","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4070-6844","authenticated-orcid":true,"given":"Yanjun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2906-8474","authenticated-orcid":true,"given":"Sujan","family":"Shresta","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6330-8841","authenticated-orcid":true,"given":"Jinsheng","family":"Wen","sequence":"additional","affiliation":[{"name":"Immunology Innovation Team, School of Medicine, Ningbo University, Ningbo, China 1"},{"name":"School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China 4"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2020,6,5]]},"reference":[{"key":"2023072617481955400_bib1","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1126\/science.aah6157","article-title":"Protective efficacy of multiple vaccine platforms against Zika virus challenge in rhesus monkeys","volume":"353","author":"Abbink","year":"2016","journal-title":"Science"},{"key":"2023072617481955400_bib2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001311","article-title":"Preexisting Japanese encephalitis virus neutralizing antibodies and increased symptomatic dengue illness in a school-based cohort in Thailand","volume":"5","author":"Anderson","year":"2011","journal-title":"PLoS Negl. 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