{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T18:18:06Z","timestamp":1778177886095,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.pntd.0014296","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000}}],"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Provincial Health Commission (Health Talents) Project","award":["No. 0720240122"],"award-info":[{"award-number":["No. 0720240122"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 82371846"],"award-info":[{"award-number":["No. 82371846"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guangdong Science and Technology Program key projects","award":["No. 2021B1212030014"],"award-info":[{"award-number":["No. 2021B1212030014"]}]},{"name":"Guangzhou Basic Research Program","award":["No. 2023A03J0810"],"award-info":[{"award-number":["No. 2023A03J0810"]}]},{"name":"Guangdong Province Basic and Applied Basic Research Fund Project","award":["No. 2024A1515010995"],"award-info":[{"award-number":["No. 2024A1515010995"]}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>\n                    Zika virus (ZIKV) is a key member of the\n                    <jats:italic>Flavivirus<\/jats:italic>\n                    genus that has emerged as a major global public health concern. The fusion loop region (residues 98\u2013110), located within domain II of the envelope protein, is highly conserved among flaviviruses, including ZIKV and Japanese encephalitis virus (JEV). However, the functional consequences of such conservation for cross-reactive immunity remains unclear. Here, we integrated bioinformatic analyses, functional assays\n                    <jats:italic>in vitro<\/jats:italic>\n                    and mouse models\n                    <jats:italic>in vivo<\/jats:italic>\n                    to systematically determine the effects of antibodies directed against the JEV fusion loop (FL) region on ZIKV infection. Sequence alignment and structural analysis revealed complete amino acid identity and almost identical three-dimensional conformations between the FL regions of the two viruses, providing a molecular basis for cross-reactivity. Antisera generated against the JEV FL region recognized ZIKV particles and displayed concentration-dependent bidirectional effects. Increased and decreased antibody levels respectively neutralized viral entry and replication, and facilitated infection\n                    <jats:italic>via<\/jats:italic>\n                    antibody-dependent enhancement (ADE). These effects were confirmed\n                    <jats:italic>in vivo<\/jats:italic>\n                    , in which high and low antibody doses reduced tissue pathology and improved survival, and increased viremia and exacerbated inflammatory responses, respectively. These findings highlight the importance of antibody concentration in determining whether cross-reactive responses to conserved structural elements engender neutralization or enhancement response. Our findings provide experimental evidence for assessing ZIKV susceptibility in JEV-vaccinated populations and offer structural insights for designing flavivirus vaccines that maximize protection while minimizing ADE risk. These findings further highlight potential pathogenic and clinical considerations for optimizing vaccine formulations to reduce cross-reactive enhancement risks.\n                  <\/jats:p>","DOI":"10.1371\/journal.pntd.0014296","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T17:48:12Z","timestamp":1777916892000},"page":"e0014296","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual role of Japanese encephalitis virus fusion loop peptide antibodies in Zika virus 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