{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T13:47:19Z","timestamp":1761745639232,"version":"3.41.2"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T00:00:00Z","timestamp":1652918400000},"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:p>In 2019, a dengue outbreak occurred with 290 confirmed cases in Wenzhou, a coastal city in southeast China. To identify the origin of the dengue virus (DENV) from this outbreak, viral RNA was extracted from four serum samples and sequenced for whole genome analysis. Then, phylogenetic analysis, gene mutation, secondary structure prediction, selection pressure analysis, and recombination analysis were performed. DENV strains Cam-03 and Cam-11 were isolated from patients traveling from Cambodia, while ZJWZ-18 and ZJWZ-62 strains were isolated from local patients without a record of traveling abroad. The whole genome sequence of all four strains was 10,735 nucleotides long. Phylogenetic tree analysis showed that the four strains belonged to genotype 1 of DENV-1, but the local Wenzhou strains and imported strains clustered in different branches. ZJWZ-18 and ZJWZ-62 were closely related to strain MF033254-Singapore-2016, and Cam-03 and Cam-11 were closely related to strain AB608788-China : Taiwan-1994. A comparison of the coding regions between the local strains and the DENV-1 standard strain (EU848545-Hawaii-1944) showed 82 amino acid mutations between the two strains. A total of 55 amino acid mutations were found between the coding regions of the local and imported strains. The overall secondary structure of the 3\u2032 UTR of the local strains had changed: apparent changes in the head and tail position were observed when compared to DENV-1 standard strain. Furthermore, selection pressure analysis and recombination detection using the 4 isolates and 41 reference strains showed two credible positive selection sites and eight credible recombination events, which warrant further studies. This study may enhance the understanding of viral replication, infection, evolution, virulence, and pathogenicity of DENV.<\/jats:p>","DOI":"10.3389\/fcimb.2022.829380","type":"journal-article","created":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T06:28:46Z","timestamp":1652941726000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Molecular Characterization and Phylogenetic Analysis of the 2019 Dengue Outbreak in Wenzhou, China"],"prefix":"10.3389","volume":"12","author":[{"given":"Axiang","family":"Han","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baochang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhewei","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuelian","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiongying","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danli","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanchun","family":"Guan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongliang","family":"Lou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.virol.2005.06.009","article-title":"Role of RNA Structures Present at the 3\u2019UTR of Dengue Virus on Translation, RNA Synthesis, and Viral Replication","volume":"339","author":"Alvarez","year":"2005","journal-title":"Virology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11262-012-0756-3","article-title":"Complete Genome Sequencing and Evolutionary Analysis of Dengue Virus Serotype 1 Isolates From an Outbreak in Kerala, South India","volume":"45","author":"Anoop","year":"2012","journal-title":"Virus Genes"},{"key":"B3","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1038\/nature12060","article-title":"The Global Distribution and Burden of Dengue","volume":"496","author":"Bhatt","year":"2013","journal-title":"Nature"},{"key":"B4","doi-asserted-by":"publisher","first-page":"3807","DOI":"10.1128\/JVI.79.6.3807-3821.2005","article-title":"Size Heterogeneity in the 3\u2019 Noncoding Region of South American Isolates of Yellow Fever Virus","volume":"79","author":"Bryant","year":"2005","journal-title":"J. Virol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1146\/annurev.mi.44.100190.003245","article-title":"Flavivirus Genome Organization, Expression, and Replication","volume":"44","author":"Chambers","year":"1990","journal-title":"Annu. Rev. Microbiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1016\/S0140-6736(15)60793-0","article-title":"Dengue Fever in China","volume":"385","author":"Chen","year":"2015","journal-title":"Lancet (Lond. Eng.)"},{"key":"B7","doi-asserted-by":"publisher","first-page":"8303","DOI":"10.1128\/JVI.79.13.8303-8315.2005","article-title":"Control of Translation by the 5\u2019- and 3\u2019-Terminal Regions of the Dengue Virus Genome","volume":"79","author":"Chiu","year":"2005","journal-title":"J. Virol."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01871-18","article-title":"Structural and Nonstructural Genes Contribute to the Genetic Diversity of RNA Viruses","volume":"9","author":"Collins","year":"2018","journal-title":"mBio"},{"key":"B9","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1093\/bioinformatics\/16.7.573","article-title":"Sister-Scanning: A Monte Carlo Procedure for Assessing Signals in Recombinant Sequences","volume":"16","author":"Gibbs","year":"2000","journal-title":"Bioinformatics"},{"key":"B10","doi-asserted-by":"publisher","first-page":"168","DOI":"10.4103\/0972-9062.242566","article-title":"Circulation of All Dengue Virus Serotypes During Dengue Outbreak in Sandakan, Sabah, Malaysia, (2016)","volume":"55","author":"Gintarong","year":"2018","journal-title":"J. Vector Borne Dis."},{"key":"B11","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1006\/viro.2002.1686","article-title":"Diversity and Evolution of the Envelope Gene of Dengue Virus Type 1","volume":"303","author":"Goncalvez","year":"2002","journal-title":"Virology"},{"key":"B12","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1128\/CMR.3.4.376","article-title":"The Dengue Viruses","volume":"3","author":"Henchal","year":"1990","journal-title":"Clin. Microbiol. Rev."},{"key":"B13","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/S1567-1348(03)00004-2","article-title":"The Origin, Emergence and Evolutionary Genetics of Dengue Virus","volume":"3","author":"Holmes","year":"2003","journal-title":"Infect. Genet. Evol."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2018.00219","article-title":"Molecular Characterization of Dengue Virus Serotype 2 Cosmospolitan Genotype From 2015 Dengue Outbreak in Yunnan, China","volume":"8","author":"Jiang","year":"2018","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"S25","DOI":"10.1016\/j.ijid.2018.12.003","article-title":"Isolation and Molecular Characterization of Dengue Virus Clinical Isolates From Pediatric Patients in New Delhi","author":"Kar","year":"2019","journal-title":"Int. J. Infect. Diseases: IJID: Off. Publ. Int. Soc. Infect. Dis."},{"key":"B16","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1093\/molbev\/mst010","article-title":"MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability","volume":"30","author":"Katoh","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1007\/s11262-011-0685-6","article-title":"Identification and Characterization of the Short Variable Region of the Japanese Encephalitis Virus 3\u2019 NTR","volume":"44","author":"Kato","year":"2012","journal-title":"Virus Genes"},{"key":"B18","doi-asserted-by":"publisher","first-page":"6567","DOI":"10.1128\/jvi.67.11.6567-6575.1993","article-title":"Genetic Determinants of Dengue Type 4 Virus Neurovirulence for Mice","volume":"67","author":"Kawano","year":"1993","journal-title":"J. Virol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1093\/molbev\/msi105","article-title":"Not So Different After All: A Comparison of Methods for Detecting Amino Acid Sites Under Selection","volume":"22","author":"Kosakovsky Pond","year":"2005","journal-title":"Mol. Biol. Evol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1016\/S0092-8674(02)00660-8","article-title":"Structure of Dengue Virus: Implications for Flavivirus Organization, Maturation, and Fusion","volume":"108","author":"Kuhn","year":"2002","journal-title":"Cell"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1093\/molbev\/msy096","article-title":"MEGA X: Molecular Evolutionary Genetics Analysis Across Computing Platforms","volume":"35","author":"Kumar","year":"2018","journal-title":"Mol. Biol. Evol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1886","DOI":"10.1017\/S0950268817000735","article-title":"Clinical, Virological and Epidemiological Characterization of Dengue Outbreak in Myanmar 2015","volume":"145","author":"Kyaw","year":"2017","journal-title":"Epidemiol. Infect."},{"key":"B23","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1093\/molbev\/msx263","article-title":"Improved Algorithmic Complexity for the 3SEQ Recombination Detection Algorithm","volume":"35","author":"Lam","year":"2018","journal-title":"Mol. Biol. Evol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"934694","DOI":"10.1155\/2010\/934694","article-title":"Characterization of Recombinant Dengue-2 Virus Derived From a Single Nucleotide Substitution in the 5\u2019 Noncoding Region","volume":"2010","author":"Leardkamolkarn","year":"2010","journal-title":"J. BioMed. Biotechnol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"vev003","DOI":"10.1093\/ve\/vev003","article-title":"RDP4: Detection and Analysis of Recombination Patterns in Virus Genomes","volume":"1","author":"Martin","year":"2015","journal-title":"Virus Evol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1089\/aid.2005.21.98","article-title":"A Modified Bootscan Algorithm for Automated Identification of Recombinant Sequences and Recombination Breakpoints","volume":"21","author":"Martin","year":"2005","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"B27","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1093\/bioinformatics\/16.6.562","article-title":"RDP: Detection of Recombination Amongst Aligned Sequences","volume":"16","author":"Martin","year":"2000","journal-title":"Bioinformatics"},{"key":"B28","doi-asserted-by":"publisher","first-page":"299","DOI":"10.2147\/CLEP.S34440","article-title":"Epidemiology of Dengue: Past, Present and Future Prospects","volume":"5","author":"Murray","year":"2013","journal-title":"Clin. Epidemiol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1093\/molbev\/mst030","article-title":"FUBAR: A Fast, Unconstrained Bayesian Approximation for Inferring Selection","volume":"30","author":"Murrell","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002764","article-title":"Detecting Individual Sites Subject to Episodic Diversifying Selection","volume":"8","author":"Murrell","year":"2012","journal-title":"PloS Genet."},{"key":"B31","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1006\/viro.1999.0056","article-title":"Possible Emergence of New Geminiviruses by Frequent Recombination","volume":"265","author":"Padidam","year":"1999","journal-title":"Virology"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0207220","article-title":"Emergence of Genotype Cosmopolitan of Dengue Virus Type 2 and Genotype III of Dengue Virus Type 3 in Thailand","volume":"13","author":"Phadungsombat","year":"2018","journal-title":"PloS One"},{"key":"B33","doi-asserted-by":"publisher","first-page":"13757","DOI":"10.1073\/pnas.241370698","article-title":"Evaluation of Methods for Detecting Recombination From DNA Sequences: Computer Simulations","volume":"98","author":"Posada","year":"2001","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B34","doi-asserted-by":"publisher","first-page":"2287","DOI":"10.1099\/0022-1317-78-9-2287","article-title":"Molecular Analysis of Dengue Virus Attenuation After Serial Passage in Primary Dog Kidney Cells","volume":"78","author":"Puri","year":"1997","journal-title":"J. Gen. Virol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"409","DOI":"10.4269\/ajtmh.15-0468","article-title":"Dissecting Japan\u2019s Dengue Outbreak in 2014","volume":"94","author":"Quam","year":"2016","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0208810","article-title":"Epidemiological Profile of Dengue in Zhejiang Province, Southeast China","volume":"13","author":"Ren","year":"2018","journal-title":"PloS One"},{"key":"B37","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/S0065-3527(03)59009-1","article-title":"Microevolution and Virulence of Dengue Viruses","volume":"59","author":"Rico-Hesse","year":"2003","journal-title":"Adv. Virus Res."},{"key":"B38","doi-asserted-by":"publisher","first-page":"2773","DOI":"10.1007\/s00018-010-0357-z","article-title":"Dengue Virus Life Cycle: Viral and Host Factors Modulating Infectivity","volume":"67","author":"Rodenhuis-Zybert","year":"2010","journal-title":"Cell. Mol. Life Sci.: CMLS"},{"key":"B39","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1186\/s12985-019-1202-0","article-title":"Multiple Introductions of Dengue Virus Strains Contribute to Dengue Outbreaks in East Kalimantan, Indonesia, in 2015-2016","volume":"16","author":"Sasmono","year":"2019","journal-title":"Virol. J."},{"key":"B40","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1038\/nrmicro2614","article-title":"Why do RNA Viruses Recombine","volume":"9","author":"Simon-Loriere","year":"2011","journal-title":"Nat. Rev. Microbiol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1007\/BF00182389","article-title":"Analyzing the Mosaic Structure of Genes","volume":"34","author":"Smith","year":"1992","journal-title":"J. Mol. Evol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.ijid.2017.02.007","article-title":"Epidemiological Trends of Dengue in Mainland China 2005-2015","volume":"57","author":"Sun","year":"2017","journal-title":"Int. J. Infect. Dis."},{"key":"B43","doi-asserted-by":"publisher","first-page":"101640","DOI":"10.1016\/j.hal.2019.101640","article-title":"Transcriptome Sequencing of a Toxic Dinoflagellate, Karenia Mikimotoi Subjected to Stress From Solar Ultraviolet Radiation","volume":"88","author":"Wang","year":"2019","journal-title":"Harmful Algae"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1670","DOI":"10.3201\/eid2109.150622","article-title":"Reemergence and Autochthonous Transmission of Dengue Virus, Eastern China 2014","volume":"21","author":"Wang","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"B45","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1016\/j.meegid.2009.02.003","article-title":"Molecular Evolution of Dengue Viruses: Contributions of Phylogenetics to Understanding the History and Epidemiology of the Preeminent Arboviral Disease","volume":"9","author":"Weaver","year":"2009","journal-title":"Infect. Genet. Evol.: J. Mol. Epidemiol. Evol Genet. Infect. Dis."},{"key":"B46","unstructured":"Dengue and Severe Dengue2015"},{"key":"B47","doi-asserted-by":"publisher","first-page":"7352","DOI":"10.1073\/pnas.96.13.7352","article-title":"Widespread Intra-Serotype Recombination in Natural Populations of Dengue Virus","volume":"96","author":"Worobey","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1959","DOI":"10.1099\/vir.0.043844-0","article-title":"A Single Nucleotide Mutation in NS2A of Japanese Encephalitis-Live Vaccine Virus (SA14-14-2) Ablates NS1\u2019 Formation and Contributes to Attenuation","volume":"93","author":"Ye","year":"2012","journal-title":"J. Gen. Virol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1126\/science.aam7120","article-title":"A Single Mutation in the prM Protein of Zika Virus Contributes to Fetal Microcephaly","volume":"358","author":"Yuan","year":"2017","journal-title":"Science"},{"key":"B50","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.ijid.2019.06.015","article-title":"Epidemiological Dynamics of Dengue Fever in Mainland China 2014-2018","volume":"86","author":"Yue","year":"2019","journal-title":"Int. J. Infect. Dis: IJID: Off. Publ. Int. Soc. Infect. Dis."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2022.829380\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T06:28:59Z","timestamp":1652941739000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2022.829380\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,19]]},"references-count":50,"alternative-id":["10.3389\/fcimb.2022.829380"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2022.829380","relation":{},"ISSN":["2235-2988"],"issn-type":[{"type":"electronic","value":"2235-2988"}],"subject":[],"published":{"date-parts":[[2022,5,19]]},"article-number":"829380"}}