{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:58:38Z","timestamp":1790434718239,"version":"4.1.0"},"reference-count":96,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T00:00:00Z","timestamp":1678320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Flaviviruses like dengue virus (DENV) and Zika virus (ZIKV) are mosquito-borne viruses that cause febrile, hemorrhagic, and neurological diseases in humans, resulting in 400 million infections annually. Due to their co-circulation in many parts of the world, flaviviruses must replicate in the presence of pre-existing adaptive immune responses targeted at serologically closely related pathogens, which can provide protection or enhance disease. However, the impact of pre-existing cross-reactive immunity as a driver of flavivirus evolution, and subsequently the implications on the emergence of immune escape variants, is poorly understood. Therefore, we investigated how replication in the presence of convalescent dengue serum drives ZIKV evolution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used an\n                      <jats:italic>in vitro<\/jats:italic>\n                      directed evolution system, passaging ZIKV in the presence of serum from humans previously infected with DENV (anti-DENV) or serum from DENV-na\u00efve patients (control serum). Following five passages in the presence of serum, we performed next-generation sequencing to identify mutations that arose during passaging. We studied two non-synonymous mutations found in the anti-DENV passaged population (E-V355I and NS1-T139A) by generating individual ZIKV mutants and assessing fitness in mammalian cells and live mosquitoes, as well as their sensitivity to antibody neutralization.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and discussion<\/jats:title>\n                    <jats:p>Both viruses had increased fitness in Vero cells with and without the addition of anti-DENV serum and in human lung epithelial and monocyte cells. In Aedes aegypti mosquitoes\u2014using blood meals with and without anti-DENV serum\u2014the mutant viruses had significantly reduced fitness compared to wild-type ZIKV. These results align with the trade-off hypothesis of constrained mosquito-borne virus evolution. Notably, only the NS1-T139A mutation escaped neutralization, while E-V335I demonstrated enhanced neutralization sensitivity to neutralization by anti-DENV serum, indicating that neutralization escape is not necessary for viruses passaged under cross-reactive immune pressures. Future studies are needed to assess cross-reactive immune selection in humans and relevant animal models or with different flaviviruses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2023.1130749","type":"journal-article","created":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T05:31:41Z","timestamp":1678339901000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Replication in the presence of dengue convalescent serum impacts Zika virus neutralization sensitivity and fitness"],"prefix":"10.3389","volume":"13","author":[{"given":"Jeffrey M.","family":"Marano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Weger-Lucarelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,9]]},"reference":[{"key":"B1","article-title":"SARS-CoV-2 mutations in MHC-I-restricted epitopes evade CD8+ T cell responses","volume-title":"Science Immunology","author":"Agerer","year":"2020"},{"key":"B2","doi-asserted-by":"publisher","first-page":"11403","DOI":"10.1128\/JVI.79.17.11403-11411.2005","article-title":"The secreted form of dengue virus nonstructural protein NS1 is endocytosed by hepatocytes and accumulates in late endosomes: Implications for viral infectivity","volume":"79","author":"Alcon-LePoder","year":"2005","journal-title":"J. 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