{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:46:05Z","timestamp":1791517565629,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.pntd.0007202","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2019,3,14]],"date-time":"2019-03-14T00:00:00Z","timestamp":1552521600000}}],"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2019,3,4]],"date-time":"2019-03-04T00:00:00Z","timestamp":1551657600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31770933 ,81471571"],"award-info":[{"award-number":["31770933 ,81471571"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81872103"],"award-info":[{"award-number":["81872103"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Colleges in Jiangsu Province","award":["17KJA310005"],"award-info":[{"award-number":["17KJA310005"]}]},{"name":"Science and Technology Climbing Fund of SIPPR","award":["PD2017-2"],"award-info":[{"award-number":["PD2017-2"]}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"DOI":"10.1371\/journal.pntd.0007202","type":"journal-article","created":{"date-parts":[[2019,3,4]],"date-time":"2019-03-04T18:34:34Z","timestamp":1551724474000},"page":"e0007202","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":24,"title":["Virulence difference of five type I dengue viruses and the intrinsic molecular mechanism"],"prefix":"10.1371","volume":"13","author":[{"given":"Chunling","family":"Zou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxiao","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qihan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1047-929X","authenticated-orcid":true,"given":"Jiufeng","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1871-8390","authenticated-orcid":true,"given":"Jianfeng","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2019,3,4]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nature12060","article-title":"The global distribution and burden of dengue","volume":"496","author":"S Bhatt","year":"2013","journal-title":"Nature"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1016\/S0140-6736(11)60470-4","article-title":"The cost of dengue control","volume":"377","author":"E Massad","year":"2011","journal-title":"Lancet"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.tim.2013.12.011","article-title":"Global spread of dengue virus types: mapping the 70 year history","volume":"22","author":"JP Messina","year":"2014","journal-title":"Trends Microbiol"},{"key":"ref4","doi-asserted-by":"crossref","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":"IA Rodenhuis-Zybert","year":"2010","journal-title":"Cell Mol Life Sci"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.mib.2011.07.012","article-title":"Exploitation of cellular pathways by Dengue virus","volume":"14","author":"W Fischl","year":"2011","journal-title":"Current Opinion in Microbiology"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1016\/j.jmb.2013.11.023","article-title":"Innate immunity to dengue virus infection and subversion of antiviral responses","volume":"426","author":"AM Green","year":"2014","journal-title":"J Mol Biol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"e00553","DOI":"10.1128\/mBio.00553-15","article-title":"Dengue Virus NS Proteins Inhibit RIG-I\/MAVS Signaling by Blocking TBK1\/IRF3 Phosphorylation: Dengue Virus Serotype 1 NS4A Is a Unique Interferon-Regulating Virulence Determinant","volume":"6","author":"NA Dalrymple","year":"2015","journal-title":"MBio"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1086\/605847","article-title":"Dengue virus NS5 inhibits interferon-alpha signaling by blocking signal transducer and activator of transcription 2 phosphorylation","volume":"200","author":"M Mazzon","year":"2009","journal-title":"J Infect Dis"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"8004","DOI":"10.1128\/JVI.79.13.8004-8013.2005","article-title":"Inhibition of alpha\/beta interferon signaling by the NS4B protein of flaviviruses","volume":"79","author":"JL Munoz-Jordan","year":"2005","journal-title":"J Virol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"e1002934","DOI":"10.1371\/journal.ppat.1002934","article-title":"DENV inhibits type I IFN production in infected cells by cleaving human STING","volume":"8","author":"S Aguirre","year":"2012","journal-title":"PLoS Pathog"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"9760","DOI":"10.1128\/JVI.01051-10","article-title":"Inhibition of the type I interferon response in human dendritic cells by dengue virus infection requires a catalytically active NS2B3 complex","volume":"84","author":"JR Rodriguez-Madoz","year":"2010","journal-title":"J Virol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"14333","DOI":"10.1073\/pnas.2335168100","article-title":"Inhibition of interferon signaling by dengue virus","volume":"100","author":"JL Munoz-Jordan","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"5408","DOI":"10.1128\/JVI.02188-08","article-title":"NS5 of dengue virus mediates STAT2 binding and degradation","volume":"83","author":"J Ashour","year":"2009","journal-title":"J Virol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1007\/s11427-014-4782-3","article-title":"Isolation and characterization of dengue virus serotype 2 from the large dengue outbreak in Guangdong, China in 2014","volume":"57","author":"H Zhao","year":"2014","journal-title":"Sci China Life Sci"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"8411","DOI":"10.1128\/JVI.00611-08","article-title":"A mouse-passaged dengue virus strain with reduced affinity for heparan sulfate causes severe disease in mice by establishing increased systemic viral loads","volume":"82","author":"TR Prestwood","year":"2008","journal-title":"J Virol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"e1624","DOI":"10.1371\/journal.pntd.0001624","article-title":"Synergistic interactions between the NS3(hel) and E proteins contribute to the virulence of dengue virus type 1","volume":"6","author":"L de Borba","year":"2012","journal-title":"PLoS Negl Trop Dis"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1006\/viro.2000.0457","article-title":"Determinants in the envelope E protein and viral RNA helicase NS3 that influence the induction of apoptosis in response to infection with dengue type 1 virus","volume":"274","author":"CN Duarte dos Santos","year":"2000","journal-title":"Virology"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"13708","DOI":"10.1128\/JVI.78.24.13708-13716.2004","article-title":"Identification of residues in the dengue virus type 2 NS2B cofactor that are critical for NS3 protease activation","volume":"78","author":"P Niyomrattanakit","year":"2004","journal-title":"J Virol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1042\/BJ20051767","article-title":"Probing the substrate specificity of the dengue virus type 2 NS3 serine protease by using internally quenched fluorescent peptides","volume":"397","author":"P Niyomrattanakit","year":"2006","journal-title":"Biochem J"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.virol.2005.06.009","article-title":"Role of RNA structures present at the 3'UTR of dengue virus on translation, RNA synthesis, and viral replication","volume":"339","author":"DE Alvarez","year":"2005","journal-title":"Virology"},{"key":"ref21","article-title":"The 5' and 3' Untranslated Regions of the Flaviviral Genome","volume":"9","author":"WC Ng","year":"2017","journal-title":"Viruses"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.meegid.2015.03.005","article-title":"Dengue is still an imported disease in China: a case study in Guangzhou","volume":"32","author":"S Sang","year":"2015","journal-title":"Infect Genet Evol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s12250-016-3872-8","article-title":"Molecular epidemiology demonstrates that imported and local strains circulated during the 2014 dengue outbreak in Guangzhou, China","volume":"32","author":"G Li","year":"2017","journal-title":"Virol Sin"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.jinf.2015.10.007","article-title":"The epidemiological characteristics and genetic diversity of dengue virus during the third largest historical outbreak of dengue in Guangdong, China, in 2014","volume":"72","author":"J Sun","year":"2016","journal-title":"J Infect"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"e0156548","DOI":"10.1371\/journal.pone.0156548","article-title":"Epidemiological and Virological Characterizations of the 2014 Dengue Outbreak in Guangzhou, China","volume":"11","author":"H Zhao","year":"2016","journal-title":"PLoS One"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"e62649","DOI":"10.1371\/journal.pone.0062649","article-title":"Worldwide spread of Dengue virus type 1","volume":"8","author":"CJ Villabona-Arenas","year":"2013","journal-title":"PLoS One"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s12916-015-0336-1","article-title":"The changing epidemiology of dengue in China, 1990\u20132014: a descriptive analysis of 25 years of nationwide surveillance data","volume":"13","author":"S Lai","year":"2015","journal-title":"BMC Med"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"209","DOI":"10.7883\/yoken.67.209","article-title":"Development of a novel Dengue-1 virus replicon system expressing secretory Gaussia luciferase for analysis of viral replication and discovery of antiviral drugs","volume":"67","author":"F Kato","year":"2014","journal-title":"Jpn J Infect Dis"},{"key":"ref29","doi-asserted-by":"crossref","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":"L Yuan","year":"2017","journal-title":"Science"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/s41467-017-02816-2","article-title":"An evolutionary NS1 mutation enhances Zika virus evasion of host interferon induction","volume":"9","author":"H Xia","year":"2018","journal-title":"Nat Commun"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.virol.2007.05.007","article-title":"Glycosylation of the dengue 2 virus E protein at N67 is critical for virus growth in vitro but not for growth in intrathoracically inoculated Aedes aegypti mosquitoes","volume":"366","author":"JE Bryant","year":"2007","journal-title":"Virology"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"114ra128","DOI":"10.1126\/scitranslmed.3003084","article-title":"Dynamics of dengue disease severity determined by the interplay between viral genetics and serotype-specific immunity","volume":"3","author":"M OhAinle","year":"2011","journal-title":"Sci Transl Med"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"4609","DOI":"10.1128\/JVI.02424-12","article-title":"Membrane topology and function of dengue virus NS2A protein","volume":"87","author":"X Xie","year":"2013","journal-title":"J Virol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.1016\/j.bbamem.2015.06.010","article-title":"Membrane topology of NS2B of dengue virus revealed by NMR spectroscopy","volume":"1848","author":"Y Li","year":"2015","journal-title":"Biochim Biophys Acta"},{"key":"ref35","article-title":"Mutagenesis of Dengue Virus Protein NS2A Revealed a Novel Domain Responsible for Virus-Induced Cytopathic Effect and Interactions between NS2A and NS2B Transmembrane Segments","volume":"91","author":"RH Wu","year":"2017","journal-title":"J Virol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1021\/acs.biochem.7b01127","article-title":"Inhibitor Bound Dengue NS2B-NS3pro Reveals Multiple Dynamic Binding Modes","volume":"57","author":"AC Gibbs","year":"2018","journal-title":"Biochemistry"},{"key":"ref37","article-title":"Isolation and propagation of mouse embryonic fibroblasts and preparation of mouse embryonic feeder layer cells","volume":"3","author":"EM A","year":"2007","journal-title":"Curr Protoc Stem Cell Biol Chapter 1: Unit1C"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.jinf.2013.05.003","article-title":"miR-146a facilitates replication of dengue virus by dampening interferon induction by targeting TRAF6","volume":"67","author":"S Wu","year":"2013","journal-title":"J Infect"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"e1007287","DOI":"10.1371\/journal.ppat.1007287","article-title":"Interferon-stimulated TRIM69 interrupts dengue virus replication by ubiquitinating viral nonstructural protein 3","volume":"14","author":"K Wang","year":"2018","journal-title":"PLoS Pathog"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"e22553","DOI":"10.1371\/journal.pone.0022553","article-title":"Enzyme-linked immunosorbent assay-format tissue culture infectious dose-50 test for titrating dengue virus","volume":"6","author":"J Li","year":"2011","journal-title":"PLoS One"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1159\/000081744","article-title":"Suckling mice were used to detect infectious dengue-2 viruses by intracerebral injection of the full-length RNA transcript","volume":"48","author":"YR Lee","year":"2005","journal-title":"Intervirology"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"45762","DOI":"10.1074\/jbc.M107360200","article-title":"Activity of recombinant dengue 2 virus NS3 protease in the presence of a truncated NS2B co-factor, small peptide substrates, and inhibitors","volume":"276","author":"D Leung","year":"2001","journal-title":"J Biol Chem"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"356","DOI":"10.3389\/fcimb.2017.00356","article-title":"DEAD-Box Helicase DDX25 Is a Negative Regulator of Type I Interferon Pathway and Facilitates RNA Virus Infection","volume":"7","author":"T Feng","year":"2017","journal-title":"Front Cell Infect Microbiol"}],"updated-by":[{"DOI":"10.1371\/journal.pntd.0007202","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2019,3,14]],"date-time":"2019-03-14T00:00:00Z","timestamp":1552521600000}}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pntd.0007202","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T04:11:00Z","timestamp":1588997460000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0007202"}},"subtitle":[],"editor":[{"given":"Walderez O.","family":"Dutra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2019,3,4]]},"references-count":43,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,3,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0007202","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pntd.0007202","asserted-by":"object"}]},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,4]]}}}