{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,14]],"date-time":"2026-11-14T01:56:07Z","timestamp":1794621367963,"version":"4.9.1"},"reference-count":82,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100000060","name":"U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI138797"],"award-info":[{"award-number":["R01 AI138797"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI153236"],"award-info":[{"award-number":["R01 AI153236"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI146917"],"award-info":[{"award-number":["R01 AI146917"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI168048"],"award-info":[{"award-number":["R01 AI168048"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI107301"],"award-info":[{"award-number":["R01 AI107301"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI181664"],"award-info":[{"award-number":["R01AI181664"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19A171401"],"award-info":[{"award-number":["U19A171401"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K22AI144050"],"award-info":[{"award-number":["K22AI144050"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Open Philantropy, Princeton Catalysis Initiative, Princeton University","id":[{"id":"https:\/\/ror.org\/00hx57361","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001021","name":"Damon Runyon Cancer Research Foundation","doi-asserted-by":"publisher","award":["DRG-2432-21"],"award-info":[{"award-number":["DRG-2432-21"]}],"id":[{"id":"10.13039\/100001021","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000152","name":"NSF | BIO | Division of Molecular and Cellular Biosciences","doi-asserted-by":"publisher","award":["NSF MCB-1942565"],"award-info":[{"award-number":["NSF MCB-1942565"]}],"id":[{"id":"10.13039\/100000152","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"U.S. Department of Health & Human Services | NIH | NIH Office of the Director","doi-asserted-by":"publisher","award":["S10OD026983"],"award-info":[{"award-number":["S10OD026983"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"U.S. Department of Health & Human Services | NIH | NIH Office of the Director","doi-asserted-by":"publisher","award":["S10OD030269"],"award-info":[{"award-number":["S10OD030269"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Microbiol"],"DOI":"10.1038\/s41564-025-02047-y","type":"journal-article","created":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T05:02:45Z","timestamp":1751950965000},"page":"1902-1917","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Amino acid changes in two viral proteins drive attenuation of the yellow fever 17D vaccine"],"prefix":"10.1038","volume":"10","author":[{"given":"Jiayu","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0252-7140","authenticated-orcid":false,"given":"Elizabeth C.","family":"Chavez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2010-9241","authenticated-orcid":false,"given":"Melina","family":"Winkler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8181-4206","authenticated-orcid":false,"given":"Jianche","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Carver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7400-4125","authenticated-orcid":false,"given":"Aaron E.","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek","family":"Biswas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1395-6610","authenticated-orcid":false,"given":"Tomokazu","family":"Tamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Tseng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danyang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8192-0162","authenticated-orcid":false,"given":"Aaron","family":"Benhamou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7027-4267","authenticated-orcid":false,"given":"Aoife K.","family":"O\u2019 Connell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao","family":"Matsuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack E.","family":"Norton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devin","family":"Kenney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9451-5819","authenticated-orcid":false,"given":"Britt","family":"Adamson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0508-9975","authenticated-orcid":false,"given":"Ralph E.","family":"Kleiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7767-022X","authenticated-orcid":false,"given":"Benjamin","family":"Burwitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3873-9188","authenticated-orcid":false,"given":"Nicholas A.","family":"Crossland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Douam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9322-7252","authenticated-orcid":false,"given":"Alexander","family":"Ploss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,8]]},"reference":[{"key":"2047_CR1","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1084\/jem.65.6.787","volume":"65","author":"M Theiler","year":"1937","unstructured":"Theiler, M. & Smith, H. H. The use of yellow fever virus modified by in vitro cultivation for human immunization. J. Exp. Med. 65, 787\u2013800 (1937).","journal-title":"J. Exp. Med."},{"key":"2047_CR2","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1084\/jem.65.6.767","volume":"65","author":"M Theiler","year":"1937","unstructured":"Theiler, M. & Smith, H. H. The effect of prolonged cultivation in vitro upon the pathogenicity of yellow fever virus. J. Exp. Med. 65, 767\u2013786 (1937).","journal-title":"J. Exp. Med."},{"key":"2047_CR3","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1016\/j.immuni.2008.02.020","volume":"28","author":"JD Miller","year":"2008","unstructured":"Miller, J. D. et al. Human effector and memory CD8+ T cell responses to smallpox and yellow fever vaccines. Immunity 28, 710\u2013722 (2008).","journal-title":"Immunity"},{"key":"2047_CR4","doi-asserted-by":"publisher","first-page":"282ra48","DOI":"10.1126\/scitranslmed.aaa3700","volume":"7","author":"SA Fuertes Marraco","year":"2015","unstructured":"Fuertes Marraco, S. A. et al. Long-lasting stem cell-like memory CD8+ T cells with a na\u00efve-like profile upon yellow fever vaccination. Sci. Transl. Med. 7, 282ra48 (2015).","journal-title":"Sci. Transl. Med."},{"key":"2047_CR5","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1126\/science.4023707","volume":"229","author":"CM Rice","year":"1985","unstructured":"Rice, C. M. et al. Nucleotide sequence of yellow fever virus: implications for flavivirus gene expression and evolution. Science 229, 726\u2013733 (1985).","journal-title":"Science"},{"key":"2047_CR6","doi-asserted-by":"publisher","first-page":"2019","DOI":"10.1073\/pnas.84.7.2019","volume":"84","author":"CS Hahn","year":"1987","unstructured":"Hahn, C. S., Dalrymple, J. M., Strauss, J. H. & Rice, C. M. Comparison of the virulent Asibi strain of yellow fever virus with the 17D vaccine strain derived from it. Proc. Natl Acad. Sci. USA 84, 2019\u20132023 (1987).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2047_CR7","doi-asserted-by":"publisher","first-page":"5676","DOI":"10.1016\/j.vaccine.2010.06.052","volume":"28","author":"D Franco","year":"2010","unstructured":"Franco, D. et al. Evaluation of yellow fever virus 17D strain as a new vector for HIV-1 vaccine development. Vaccine 28, 5676\u20135685 (2010).","journal-title":"Vaccine"},{"key":"2047_CR8","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1038\/s41586-020-3035-9","volume":"590","author":"L Sanchez-Felipe","year":"2021","unstructured":"Sanchez-Felipe, L. et al. A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate. Nature 590, 320\u2013325 (2021).","journal-title":"Nature"},{"key":"2047_CR9","doi-asserted-by":"publisher","first-page":"e1001005","DOI":"10.1371\/journal.ppat.1001005","volume":"6","author":"AS Lauring","year":"2010","unstructured":"Lauring, A. S. & Andino, R. Quasispecies theory and the behavior of RNA viruses. PLoS Pathog. 6, e1001005 (2010).","journal-title":"PLoS Pathog."},{"key":"2047_CR10","doi-asserted-by":"publisher","first-page":"e3295","DOI":"10.1371\/journal.pntd.0003295","volume":"8","author":"F Engelmann","year":"2014","unstructured":"Engelmann, F. et al. Pathophysiologic and transcriptomic analyses of viscerotropic yellow fever in a rhesus macaque model. PLoS Negl. Trop. Dis. 8, e3295 (2014).","journal-title":"PLoS Negl. Trop. Dis."},{"key":"2047_CR11","doi-asserted-by":"publisher","first-page":"eade5795","DOI":"10.1126\/scitranslmed.ade5795","volume":"15","author":"MJ Ricciardi","year":"2023","unstructured":"Ricciardi, M. J. et al. Therapeutic neutralizing monoclonal antibody administration protects against lethal yellow fever virus infection. Sci. Transl. Med. 15, eade5795 (2023).","journal-title":"Sci. Transl. Med."},{"key":"2047_CR12","doi-asserted-by":"publisher","first-page":"eadf5494","DOI":"10.1126\/scisignal.adf5494","volume":"16","author":"EV Mesev","year":"2023","unstructured":"Mesev, E. V. et al. Membrane-proximal motifs encode differences in signaling strength between type I and III interferon receptors. Sci. Signal. 16, eadf5494 (2023).","journal-title":"Sci. Signal."},{"key":"2047_CR13","doi-asserted-by":"publisher","first-page":"2119","DOI":"10.1590\/0001-3765201720160196","volume":"89","author":"TC Kassar","year":"2017","unstructured":"Kassar, T. C. et al. Construction and characterization of a recombinant yellow fever virus stably expressing Gaussia luciferase. An. Acad. Bras. Cienc. 89, 2119\u20132130 (2017).","journal-title":"An. Acad. Bras. Cienc."},{"key":"2047_CR14","doi-asserted-by":"publisher","first-page":"e20202486","DOI":"10.1084\/jem.20202486","volume":"218","author":"P Bastard","year":"2021","unstructured":"Bastard, P. et al. Auto-antibodies to type I IFNs can underlie adverse reactions to yellow fever live attenuated vaccine. J. Exp. Med. 218, e20202486 (2021).","journal-title":"J. Exp. Med."},{"key":"2047_CR15","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1080\/22221751.2021.2021808","volume":"11","author":"T Tamura","year":"2022","unstructured":"Tamura, T. et al. Generation and characterization of genetically and antigenically diverse infectious clones of dengue virus serotypes 1\u20134. Emerg. Microbes Infect. 11, 227\u2013239 (2022).","journal-title":"Emerg. Microbes Infect."},{"key":"2047_CR16","doi-asserted-by":"publisher","first-page":"2367","DOI":"10.1128\/JVI.03162-12","volume":"87","author":"J Edmonds","year":"2013","unstructured":"Edmonds, J. et al. A novel bacterium-free method for generation of flavivirus infectious DNA by circular polymerase extension reaction allows accurate recapitulation of viral heterogeneity. J. Virol. 87, 2367\u20132372 (2013).","journal-title":"J. Virol."},{"key":"2047_CR17","doi-asserted-by":"publisher","first-page":"1643","DOI":"10.1038\/nprot.2015.103","volume":"10","author":"MJ Smola","year":"2015","unstructured":"Smola, M. J., Rice, G. M., Busan, S., Siegfried, N. A. & Weeks, K. M. Selective 2\u2032-hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP) for direct, versatile and accurate RNA structure analysis. Nat. Protoc. 10, 1643\u20131669 (2015).","journal-title":"Nat. Protoc."},{"key":"2047_CR18","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1038\/nmeth.3029","volume":"11","author":"NA Siegfried","year":"2014","unstructured":"Siegfried, N. A., Busan, S., Rice, G. M., Nelson, J. A. E. & Weeks, K. M. RNA motif discovery by SHAPE and mutational profiling (SHAPE-MaP). Nat. Methods 11, 959\u2013965 (2014).","journal-title":"Nat. Methods"},{"key":"2047_CR19","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09391-8","volume":"10","author":"RG Huber","year":"2019","unstructured":"Huber, R. G. et al. Structure mapping of dengue and Zika viruses reveals functional long-range interactions. Nat. Commun. 10, 1408 (2019).","journal-title":"Nat. Commun."},{"key":"2047_CR20","doi-asserted-by":"publisher","first-page":"12436","DOI":"10.1093\/nar\/gkaa1053","volume":"48","author":"I Manfredonia","year":"2020","unstructured":"Manfredonia, I. et al. Genome-wide mapping of SARS-CoV-2 RNA structures identifies therapeutically-relevant elements. Nucleic Acids Res. 48, 12436\u201312452 (2020).","journal-title":"Nucleic Acids Res."},{"key":"2047_CR21","doi-asserted-by":"publisher","first-page":"e2217053120","DOI":"10.1073\/pnas.2217053120","volume":"120","author":"MA Boerneke","year":"2023","unstructured":"Boerneke, M. A., Gokhale, N. S., Horner, S. M. & Weeks, K. M. Structure-first identification of RNA elements that regulate dengue virus genome architecture and replication. Proc. Natl Acad. Sci. USA 120, e2217053120 (2023).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2047_CR22","doi-asserted-by":"publisher","first-page":"e34","DOI":"10.1093\/nar\/gkaa1255","volume":"49","author":"T Marinus","year":"2021","unstructured":"Marinus, T., Fessler, A. B., Ogle, C. A. & Incarnato, D. A novel SHAPE reagent enables the analysis of RNA structure in living cells with unprecedented accuracy. Nucleic Acids Res. 49, e34 (2021).","journal-title":"Nucleic Acids Res."},{"key":"2047_CR23","doi-asserted-by":"publisher","first-page":"e97","DOI":"10.1093\/nar\/gky486","volume":"46","author":"D Incarnato","year":"2018","unstructured":"Incarnato, D., Morandi, E., Simon, L. M. & Oliviero, S. RNA Framework: an all-in-one toolkit for the analysis of RNA structures and post-transcriptional modifications. Nucleic Acids Res. 46, e97 (2018).","journal-title":"Nucleic Acids Res."},{"key":"2047_CR24","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.tim.2016.01.002","volume":"24","author":"SM Villordo","year":"2016","unstructured":"Villordo, S. M., Carballeda, J. M., Filomatori, C. V. & Gamarnik, A. V. RNA structure duplications and flavivirus host adaptation. Trends Microbiol. 24, 270\u2013283 (2016).","journal-title":"Trends Microbiol."},{"key":"2047_CR25","doi-asserted-by":"publisher","first-page":"2689","DOI":"10.1128\/JVI.79.5.2689-2699.2005","volume":"79","author":"R Sumpter Jr","year":"2005","unstructured":"Sumpter, R. Jr et al. Regulating intracellular antiviral defense and permissiveness to hepatitis C virus RNA replication through a cellular RNA helicase, RIG-I. J. Virol. 79, 2689\u20132699 (2005).","journal-title":"J. Virol."},{"key":"2047_CR26","doi-asserted-by":"publisher","first-page":"16739","DOI":"10.1074\/jbc.M414139200","volume":"280","author":"K Li","year":"2005","unstructured":"Li, K., Chen, Z., Kato, N., Gale, M. Jr & Lemon, S. M. Distinct poly(I-C) and virus-activated signaling pathways leading to interferon-beta production in hepatocytes. J. Biol. Chem. 280, 16739\u201316747 (2005).","journal-title":"J. Biol. Chem."},{"key":"2047_CR27","doi-asserted-by":"publisher","first-page":"9824","DOI":"10.1128\/JVI.01125-09","volume":"83","author":"N Wang","year":"2009","unstructured":"Wang, N. et al. Toll-like receptor 3 mediates establishment of an antiviral state against hepatitis C virus in hepatoma cells. J. Virol. 83, 9824\u20139834 (2009).","journal-title":"J. Virol."},{"key":"2047_CR28","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.virol.2016.05.019","volume":"496","author":"EA Voigt","year":"2016","unstructured":"Voigt, E. A., Swick, A. & Yin, J. Rapid induction and persistence of paracrine-induced cellular antiviral states arrest viral infection spread in A549 cells. Virology 496, 59\u201366 (2016).","journal-title":"Virology"},{"key":"2047_CR29","doi-asserted-by":"publisher","first-page":"3109","DOI":"10.1182\/blood-2009-04-214957","volume":"115","author":"A Quint\u00e1s-Cardama","year":"2010","unstructured":"Quint\u00e1s-Cardama, A. et al. Preclinical characterization of the selective JAK1\/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood 115, 3109\u20133117 (2010).","journal-title":"Blood"},{"key":"2047_CR30","doi-asserted-by":"publisher","first-page":"236","DOI":"10.4049\/jimmunol.107.1.236","volume":"107","author":"B Zisman","year":"1971","unstructured":"Zisman, B., Wheelock, E. F. & Allison, A. C. Role of macrophages and antibody in resistance of mice against yellow fever virus. J. Immunol. 107, 236\u2013243 (1971).","journal-title":"J. Immunol."},{"key":"2047_CR31","doi-asserted-by":"publisher","first-page":"299","DOI":"10.4269\/ajtmh.1941.s1-21.299","volume":"s1-21","author":"JC Bugher","year":"1941","unstructured":"Bugher, J. C. The use of baby mice in yellow fever studies. Am. J. Trop. Med. Hyg. s1-21, 299\u2013307 (1941).","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"2047_CR32","doi-asserted-by":"publisher","first-page":"e1000614","DOI":"10.1371\/journal.ppat.1000614","volume":"5","author":"KC Meier","year":"2009","unstructured":"Meier, K. C., Gardner, C. L., Khoretonenko, M. V., Klimstra, W. B. & Ryman, K. D. A mouse model for studying viscerotropic disease caused by yellow fever virus infection. PLoS Pathog. 5, e1000614 (2009).","journal-title":"PLoS Pathog."},{"key":"2047_CR33","doi-asserted-by":"publisher","first-page":"e00819-","DOI":"10.1128\/mBio.00819-17","volume":"8","author":"F Douam","year":"2017","unstructured":"Douam, F. et al. Type III interferon-mediated signaling is critical for controlling live attenuated yellow fever virus infection. mBio 8, e00819-17 (2017).","journal-title":"mBio"},{"key":"2047_CR34","doi-asserted-by":"publisher","first-page":"32648","DOI":"10.1073\/pnas.2014096117","volume":"117","author":"AL Bailey","year":"2020","unstructured":"Bailey, A. L. et al. Consumptive coagulopathy of severe yellow fever occurs independently of hepatocellular tropism and massive hepatic injury. Proc. Natl Acad. Sci. USA 117, 32648\u201332656 (2020).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2047_CR35","doi-asserted-by":"publisher","first-page":"e01956-","DOI":"10.1128\/mBio.01956-15","volume":"7","author":"MD Fernandez-Garcia","year":"2016","unstructured":"Fernandez-Garcia, M. D. et al. Vaccine and wild-type strains of yellow fever virus engage distinct entry mechanisms and differentially stimulate antiviral immune responses. mBio 7, e01956-15 (2016).","journal-title":"mBio"},{"key":"2047_CR36","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1038\/ni.1688","volume":"10","author":"TD Querec","year":"2009","unstructured":"Querec, T. D. et al. Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans. Nat. Immunol. 10, 116\u2013125 (2009).","journal-title":"Nat. Immunol."},{"key":"2047_CR37","doi-asserted-by":"publisher","first-page":"3119","DOI":"10.1084\/jem.20082292","volume":"205","author":"D Gaucher","year":"2008","unstructured":"Gaucher, D. et al. Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses. J. Exp. Med. 205, 3119\u20133131 (2008).","journal-title":"J. Exp. Med."},{"key":"2047_CR38","doi-asserted-by":"publisher","first-page":"1476","DOI":"10.4049\/jimmunol.1700083","volume":"199","author":"J Hou","year":"2017","unstructured":"Hou, J. et al. A systems vaccinology approach reveals temporal transcriptomic changes of immune responses to the yellow fever 17D vaccine. J. Immunol. 199, 1476\u20131489 (2017).","journal-title":"J. Immunol."},{"key":"2047_CR39","doi-asserted-by":"publisher","first-page":"e0151623","DOI":"10.1128\/jvi.01516-23","volume":"98","author":"N Mantel","year":"2024","unstructured":"Mantel, N. et al. Cynomolgus macaques as a translational model of human immune responses to yellow fever 17D vaccination. J. Virol. 98, e0151623 (2024).","journal-title":"J. Virol."},{"key":"2047_CR40","doi-asserted-by":"crossref","unstructured":"Gon\u00e7alves, A. N. A. et al. Systems immunology approaches to understanding immune responses in acute infection of yellow fever patients. J. Med. Virol. 96, e70099 (2024).","DOI":"10.1002\/jmv.70099"},{"key":"2047_CR41","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1016\/j.tim.2018.05.012","volume":"26","author":"F Douam","year":"2018","unstructured":"Douam, F. & Ploss, A. Yellow fever virus: knowledge gaps impeding the fight against an old foe. Trends Microbiol. 26, 913\u2013928 (2018).","journal-title":"Trends Microbiol."},{"key":"2047_CR42","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1016\/j.vaccine.2022.11.051","volume":"41","author":"F Piras-Douce","year":"2023","unstructured":"Piras-Douce, F. et al. Evaluation of safety and immuno-efficacy of a next generation live-attenuated yellow fever vaccine in cynomolgus macaques. Vaccine 41, 1457\u20131470 (2023).","journal-title":"Vaccine"},{"key":"2047_CR43","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1089\/vbz.2019.2495","volume":"20","author":"MA McArthur","year":"2020","unstructured":"McArthur, M. A., Zhang, S. L., Li, L., Tesh, R. B. & Barrett, A. D. T. Molecular characterization of hamster-adapted yellow fever virus. Vector Borne Zoonotic Dis. 20, 222\u2013227 (2020).","journal-title":"Vector Borne Zoonotic Dis."},{"key":"2047_CR44","doi-asserted-by":"publisher","first-page":"6024","DOI":"10.1128\/JVI.02509-07","volume":"82","author":"E Lee","year":"2008","unstructured":"Lee, E. & Lobigs, M. E protein domain III determinants of yellow fever virus 17D vaccine strain enhance binding to glycosaminoglycans, impede virus spread, and attenuate virulence. J. Virol. 82, 6024\u20136033 (2008).","journal-title":"J. Virol."},{"key":"2047_CR45","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-022-00460-6","volume":"7","author":"EH Davis","year":"2022","unstructured":"Davis, E. H. et al. Impact of yellow fever virus envelope protein on wild-type and vaccine epitopes and tissue tropism. npj Vaccines 7, 39 (2022).","journal-title":"npj Vaccines"},{"key":"2047_CR46","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.02424-12","author":"X Xie","year":"2013","unstructured":"Xie, X., Gayen, S., Kang, C., Yuan, Z. & Shi, P.-Y. Membrane topology and function of dengue virus NS2A protein. J. Virol. https:\/\/doi.org\/10.1128\/jvi.02424-12 (2013).","journal-title":"J. Virol."},{"key":"2047_CR47","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.coviro.2014.09.020","volume":"9","author":"S Apte-Sengupta","year":"2014","unstructured":"Apte-Sengupta, S., Sirohi, D. & Kuhn, R. J. Coupling of replication and assembly in flaviviruses. Curr. Opin. Virol. 9, 134\u2013142 (2014).","journal-title":"Curr. Opin. Virol."},{"key":"2047_CR48","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.01047-19","author":"B Monel","year":"2019","unstructured":"Monel, B. et al. Atlastin endoplasmic reticulum-shaping proteins facilitate Zika virus replication. J. Virol. https:\/\/doi.org\/10.1128\/jvi.01047-19 (2019).","journal-title":"J. Virol."},{"key":"2047_CR49","doi-asserted-by":"publisher","first-page":"4773","DOI":"10.1128\/JVI.76.10.4773-4784.2002","volume":"76","author":"BM K\u00fcmmerer","year":"2002","unstructured":"K\u00fcmmerer, B. M. & Rice, C. M. Mutations in the yellow fever virus nonstructural protein NS2A selectively block production of infectious particles. J. Virol. 76, 4773\u20134784 (2002).","journal-title":"J. Virol."},{"key":"2047_CR50","doi-asserted-by":"publisher","first-page":"4731","DOI":"10.1128\/JVI.00002-08","volume":"82","author":"JY Leung","year":"2008","unstructured":"Leung, J. Y. et al. Role of nonstructural protein NS2A in flavivirus assembly. J. Virol. 82, 4731\u20134741 (2008).","journal-title":"J. Virol."},{"key":"2047_CR51","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1016\/j.chom.2019.09.015","volume":"26","author":"X Xie","year":"2019","unstructured":"Xie, X. et al. Dengue NS2A protein orchestrates virus assembly. Cell Host Microbe 26, 606\u2013622.e8 (2019).","journal-title":"Cell Host Microbe"},{"key":"2047_CR52","doi-asserted-by":"publisher","first-page":"12225","DOI":"10.1128\/JVI.78.22.12225-12235.2004","volume":"78","author":"WJ Liu","year":"2004","unstructured":"Liu, W. J., Chen, H. B., Wang, X. J., Huang, H. & Khromykh, A. A. Analysis of adaptive mutations in Kunjin virus replicon RNA reveals a novel role for the flavivirus nonstructural protein NS2A in inhibition of beta interferon promoter-driven transcription. J. Virol. 78, 12225\u201312235 (2004).","journal-title":"J. Virol."},{"key":"2047_CR53","doi-asserted-by":"publisher","first-page":"2396","DOI":"10.1128\/JVI.80.5.2396-2404.2006","volume":"80","author":"WJ Liu","year":"2006","unstructured":"Liu, W. J. et al. A single amino acid substitution in the West Nile virus nonstructural protein NS2A disables its ability to inhibit alpha\/beta interferon induction and attenuates virus virulence in mice. J. Virol. 80, 2396\u20132404 (2006).","journal-title":"J. Virol."},{"key":"2047_CR54","doi-asserted-by":"publisher","first-page":"10347","DOI":"10.1128\/JVI.00525-12","volume":"86","author":"Y-C Tu","year":"2012","unstructured":"Tu, Y.-C. et al. Blocking double-stranded RNA-activated protein kinase PKR by Japanese encephalitis virus nonstructural protein 2A. J. Virol. 86, 10347\u201310358 (2012).","journal-title":"J. Virol."},{"key":"2047_CR55","doi-asserted-by":"publisher","first-page":"e1012561","DOI":"10.1371\/journal.ppat.1012561","volume":"21","author":"SG Muccilli","year":"2025","unstructured":"Muccilli, S. G. et al. Mitochondrial hyperactivity and reactive oxygen species drive innate immunity to the yellow fever virus-17D live-attenuated vaccine. PLoS Pathog. 21, e1012561 (2025).","journal-title":"PLoS Pathog."},{"key":"2047_CR56","doi-asserted-by":"publisher","first-page":"3095","DOI":"10.1128\/JVI.73.4.3095-3101.1999","volume":"73","author":"TJ Chambers","year":"1999","unstructured":"Chambers, T. J., Nestorowicz, A., Mason, P. W. & Rice, C. M. Yellow fever\/Japanese encephalitis chimeric viruses: construction and biological properties. J. Virol. 73, 3095\u20133101 (1999).","journal-title":"J. Virol."},{"key":"2047_CR57","doi-asserted-by":"publisher","first-page":"6328","DOI":"10.1128\/JVI.00219-15","volume":"89","author":"GD Gromowski","year":"2015","unstructured":"Gromowski, G. D., Firestone, C.-Y. & Whitehead, S. S. Genetic determinants of Japanese encephalitis virus vaccine strain SA14-14-2 that govern attenuation of virulence in mice. J. Virol. 89, 6328\u20136337 (2015).","journal-title":"J. Virol."},{"key":"2047_CR58","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0519-7","volume":"15","author":"CB Matranga","year":"2014","unstructured":"Matranga, C. B. et al. Enhanced methods for unbiased deep sequencing of Lassa and Ebola RNA viruses from clinical and biological samples. Genome Biol. 15, 519 (2014).","journal-title":"Genome Biol."},{"key":"2047_CR59","doi-asserted-by":"publisher","unstructured":"Gnirke, A. et al. Solution hybrid selection with ultra-long oligonucleotides for massively parallel targeted sequencing. Nat. Biotechnol. https:\/\/doi.org\/10.1038\/nbt.1523 (2009).","DOI":"10.1038\/nbt.1523"},{"key":"2047_CR60","doi-asserted-by":"publisher","unstructured":"Park, D. et al. broadinstitute\/viral-pipelines: v2.4.1.0. Zenodo https:\/\/doi.org\/10.5281\/zenodo.15177514 (2025).","DOI":"10.5281\/zenodo.15177514"},{"key":"2047_CR61","doi-asserted-by":"publisher","unstructured":"Park, D. et al. (2019). broadinstitute\/viral-ngs: v1.25.0 (v1.25.0). Zenodo https:\/\/doi.org\/10.5281\/zenodo.3509008 (2019).","DOI":"10.5281\/zenodo.3509008"},{"key":"2047_CR62","doi-asserted-by":"publisher","first-page":"e102","DOI":"10.1002\/cpbi.102","volume":"70","author":"A Prjibelski","year":"2020","unstructured":"Prjibelski, A., Antipov, D., Meleshko, D., Lapidus, A. & Korobeynikov, A. Using SPAdes De Novo Assembler. Curr. Protoc. Bioinformatics 70, e102 (2020).","journal-title":"Curr. Protoc. Bioinformatics"},{"key":"2047_CR63","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-14-674","volume":"14","author":"X Yang","year":"2013","unstructured":"Yang, X., Charlebois, P., Macalalad, A., Henn, M. R. & Zody, M. C. V-Phaser 2: variant inference for viral populations. BMC Genomics 14, 674 (2013).","journal-title":"BMC Genomics"},{"key":"2047_CR64","doi-asserted-by":"crossref","unstructured":"Edgar, R. C. MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics 5, 113 (2004).","DOI":"10.1186\/1471-2105-5-113"},{"key":"2047_CR65","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.1016\/j.cell.2015.05.002","volume":"161","author":"EZ Macosko","year":"2015","unstructured":"Macosko, E. Z. et al. Highly parallel genome-wide expression profiling of individualcells using nanoliter droplets. Cell 161, 1202\u20131214 (2015).","journal-title":"Cell"},{"key":"2047_CR66","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1038\/s41587-019-0201-4","volume":"37","author":"D Kim","year":"2019","unstructured":"Kim, D., Paggi, J. M., Park, C., Bennett, C. & Salzberg, S. L. Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype. Nat. Biotechnol. 37, 907\u2013915 (2019).","journal-title":"Nat. Biotechnol."},{"key":"2047_CR67","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","volume":"31","author":"S Anders","year":"2015","unstructured":"Anders, S., Pyl, P. T. & Huber, W. HTSeq\u2014a Python framework to work with high-throughput sequencing data. Bioinformatics 31, 166\u2013169 (2015).","journal-title":"Bioinformatics"},{"key":"2047_CR68","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1186\/s12859-020-3433-x","volume":"21","author":"X Zhang","year":"2020","unstructured":"Zhang, X. & Jonassen, I. RASflow: an RNA-Seq analysis workflow with Snakemake. BMC Bioinf. 21, 110 (2020).","journal-title":"BMC Bioinf."},{"key":"2047_CR69","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).","journal-title":"Genome Biol."},{"key":"2047_CR70","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","volume":"16","author":"G Yu","year":"2012","unstructured":"Yu, G., Wang, L.-G., Han, Y. & He, Q.-Y. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 16, 284\u2013287 (2012).","journal-title":"OMICS"},{"key":"2047_CR71","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","volume":"1","author":"A Liberzon","year":"2015","unstructured":"Liberzon, A. et al. The Molecular Signatures Database (MSigDB) hallmark gene set collection. Cell Syst. 1, 417\u2013425 (2015).","journal-title":"Cell Syst."},{"key":"2047_CR72","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giab008","volume":"10","author":"P Danecek","year":"2021","unstructured":"Danecek, P. et al. Twelve years of SAMtools and BCFtools. Gigascience 10, giab008 (2021).","journal-title":"Gigascience"},{"key":"2047_CR73","doi-asserted-by":"publisher","first-page":"1974","DOI":"10.1093\/bioinformatics\/btp250","volume":"25","author":"K Darty","year":"2009","unstructured":"Darty, K., Denise, A. & Ponty, Y. VARNA: interactive drawing and editing of the RNA secondary structure. Bioinformatics 25, 1974\u20131975 (2009).","journal-title":"Bioinformatics"},{"key":"2047_CR74","doi-asserted-by":"publisher","first-page":"e1005600","DOI":"10.1371\/journal.ppat.1005600","volume":"12","author":"J-D Lin","year":"2016","unstructured":"Lin, J.-D. et al. Distinct roles of type I and type III interferons in intestinal immunity to homologous and heterologous rotavirus infections. PLoS Pathog. 12, e1005600 (2016).","journal-title":"PLoS Pathog."},{"key":"2047_CR75","doi-asserted-by":"crossref","first-page":"254ra129","DOI":"10.1126\/scitranslmed.3009512","volume":"6","author":"YP de Jong","year":"2014","unstructured":"de Jong, Y. P. et al. Broadly neutralizing antibodies abrogate established hepatitis C virus infection. Sci. Transl. Med. 6, 254ra129 (2014).","journal-title":"Sci. Transl. Med."},{"key":"2047_CR76","doi-asserted-by":"publisher","first-page":"100535","DOI":"10.1016\/j.jhepr.2022.100535","volume":"4","author":"Y Liu","year":"2022","unstructured":"Liu, Y. et al. Molecular clones of genetically distinct hepatitis B virus genotypes reveal distinct host and drug treatment responses. JHEP Rep. 4, 100535 (2022).","journal-title":"JHEP Rep."},{"key":"2047_CR77","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1038\/s41586-018-0121-3","volume":"557","author":"R Zhang","year":"2018","unstructured":"Zhang, R. et al. Mxra8 is a receptor for multiple arthritogenic alphaviruses. Nature 557, 570\u2013574 (2018).","journal-title":"Nature"},{"key":"2047_CR78","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1038\/s41586-021-04326-0","volume":"602","author":"LE Clark","year":"2022","unstructured":"Clark, L. E. et al. VLDLR and ApoER2 are receptors for multiple alphaviruses. Nature 602, 475\u2013480 (2022).","journal-title":"Nature"},{"key":"2047_CR79","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14781","volume":"8","author":"F Douam","year":"2017","unstructured":"Douam, F. et al. Single-cell tracking of flavivirus RNA uncovers species-specific interactions with the immune system dictating disease outcome. Nat. Commun. 8, 14781 (2017).","journal-title":"Nat. Commun."},{"key":"2047_CR80","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07478-2","volume":"9","author":"F Douam","year":"2018","unstructured":"Douam, F. et al. Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses. Nat. Commun. 9, 5031 (2018).","journal-title":"Nat. Commun."},{"key":"2047_CR81","doi-asserted-by":"publisher","unstructured":"Zhang, J. et al. The molecular basis for the attenuation of the yellow fever 17D vaccine [Data set]. Version 1. Princeton DataCommons https:\/\/doi.org\/10.34770\/69g9-rb48 (2025).","DOI":"10.34770\/69g9-rb48"},{"key":"2047_CR82","doi-asserted-by":"publisher","unstructured":"Biswas, A. & Zhang, J. Yellow fever protein variation analysis script. Zenodo https:\/\/doi.org\/10.5281\/ZENODO.15400604 (2025).","DOI":"10.5281\/ZENODO.15400604"}],"container-title":["Nature Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41564-025-02047-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41564-025-02047-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41564-025-02047-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T00:31:55Z","timestamp":1757205115000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41564-025-02047-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,8]]},"references-count":82,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["2047"],"URL":"https:\/\/doi.org\/10.1038\/s41564-025-02047-y","relation":{},"ISSN":["2058-5276"],"issn-type":[{"value":"2058-5276","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,8]]},"assertion":[{"value":"3 October 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"B.A. is an advisory board member with options for Arbor Biotechnologies and Tessera Therapeutics. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}