{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T00:16:46Z","timestamp":1793060206496,"version":"4.5.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T00:00:00Z","timestamp":1740009600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T00:00:00Z","timestamp":1740009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC113-2327-B-006-002-"],"award-info":[{"award-number":["NSTC113-2327-B-006-002-"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC113-2321-B-006-007-"],"award-info":[{"award-number":["NSTC113-2321-B-006-007-"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["NHRI-MR-113-GP-06"],"award-info":[{"award-number":["NHRI-MR-113-GP-06"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"crossref","award":["NHRI-IV-113-PP-11"],"award-info":[{"award-number":["NHRI-IV-113-PP-11"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Cheng Kung University and National Health Research Institutes","award":["NHRI-NCKUMC-11301"],"award-info":[{"award-number":["NHRI-NCKUMC-11301"]}]},{"DOI":"10.13039\/501100007750","name":"National Cheng Kung University","doi-asserted-by":"publisher","award":["D113-F1737"],"award-info":[{"award-number":["D113-F1737"]}],"id":[{"id":"10.13039\/501100007750","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Biomed Sci"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The largest dengue virus 2 (DENV2) outbreak occurred in Taiwan in 2015, resulting in many fatalities. We therefore aim to identify crucial genetic variations which determine the virulence of the 2015 Taiwan outbreak strains.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We compared the 2015 Taiwan DENV2 sequences to the pre-2015 sequences. Reverse genetics (rg) viruses with substitutions were produced and the viral growth kinetics were investigated. We treated A549 cells with interferon (IFN) to determine the interferon-stimulated genes (ISGs) expression and STAT1 phosphorylation in the rg viral infection and plasmid transfection systems. IFN and pro-inflammatory cytokines levels were measured upon DENV infection using ELISA.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The rgNS1-K272R mutant showed faster replication in IFN-I producing cells compared to wildtype (WT) virus. Results revealed that NS1-K272R substitution contributed to higher soluble NS1 secretion and evade the antiviral response by suppressing the expression of ISGs and STAT1 phosphorylation compared to NS1-WT. Infection with rgNS1-K272R induced higher secretion of pro-inflammatory cytokines through the activation of canonical nuclear factor-kappa B (NF-\u03baB) signaling pathway.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our results revealed that the DENV NS1 amino acid substitution affects the NS1 ability in immune evasion, which may contribute to the largest dengue outbreak in Taiwan since the 1990s.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12929-024-01116-4","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T00:01:41Z","timestamp":1740009701000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A non-structural protein 1 substitution of dengue virus enhances viral replication by interfering with the antiviral signaling pathway"],"prefix":"10.1186","volume":"32","author":[{"given":"Jing-Ru","family":"Hee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayna","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Hong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Hsuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiao-Hsuan","family":"Chao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Wen","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pin","family":"Ling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Wen","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Peng","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin Jang Hann","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trai-Ming","family":"Yeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4127-4046","authenticated-orcid":false,"given":"Jen-Ren","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,20]]},"reference":[{"issue":"2","key":"1116_CR1","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1111\/j.1574-695X.2010.00670.x","volume":"59","author":"A Jain","year":"2010","unstructured":"Jain A, Chaturvedi UC. Dengue in infants: an overview. FEMS Immunol Med Microbiol. 2010;59(2):119\u201330.","journal-title":"FEMS Immunol Med Microbiol"},{"key":"1116_CR2","doi-asserted-by":"publisher","DOI":"10.1590\/0037-8682-0290-2021","volume":"55","author":"YHM Hokerberg","year":"2022","unstructured":"Hokerberg YHM, Kohn F, Souza TS, Passos SRL. Clinical profile of dengue in the elderly using surveillance data from two epidemics. Rev Soc Bras Med Trop. 2022;55: e0290.","journal-title":"Rev Soc Bras Med Trop"},{"issue":"8","key":"1116_CR3","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1086\/343813","volume":"186","author":"DH Libraty","year":"2002","unstructured":"Libraty DH, Young PR, Pickering D, Endy TP, Kalayanarooj S, Green S, et al. High circulating levels of the dengue virus nonstructural protein NS1 early in dengue illness correlate with the development of dengue hemorrhagic fever. J Infect Dis. 2002;186(8):1165\u20138.","journal-title":"J Infect Dis"},{"key":"1116_CR4","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1186\/s12879-014-0570-8","volume":"14","author":"SA Paranavitane","year":"2014","unstructured":"Paranavitane SA, Gomes L, Kamaladasa A, Adikari TN, Wickramasinghe N, Jeewandara C, et al. Dengue NS1 antigen as a marker of severe clinical disease. BMC Infect Dis. 2014;14:570.","journal-title":"BMC Infect Dis"},{"issue":"9","key":"1116_CR5","doi-asserted-by":"publisher","first-page":"946","DOI":"10.3390\/vaccines9090946","volume":"9","author":"G Lebeau","year":"2021","unstructured":"Lebeau G, Lagrave A, Ogire E, Grondin L, Seriacaroupin S, Moutoussamy C, et al. Viral toxin NS1 implication in dengue pathogenesis making it a pivotal target in development of efficient vaccine. Vaccines. 2021;9(9):946.","journal-title":"Vaccines"},{"issue":"2","key":"1116_CR6","doi-asserted-by":"publisher","first-page":"364","DOI":"10.3390\/v15020364","volume":"15","author":"DE Safadi","year":"2023","unstructured":"Safadi DE, Lebeau G, Lagrave A, Melade J, Grondin L, Rosanaly S, et al. Extracellular vesicles are conveyors of the NS1 toxin during dengue virus and Zika virus infection. Viruses. 2023;15(2):364.","journal-title":"Viruses"},{"key":"1116_CR7","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.virol.2016.06.008","volume":"496","author":"F Alayli","year":"2016","unstructured":"Alayli F, Scholle F. Dengue virus NS1 enhances viral replication and pro-inflammatory cytokine production in human dendritic cells. Virology. 2016;496:227\u201336.","journal-title":"Virology"},{"issue":"304","key":"1116_CR8","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaa3863","volume":"7","author":"N Modhiran","year":"2015","unstructured":"Modhiran N, Watterson D, Muller DA, Panetta AK, Sester DP, Liu L, et al. Dengue virus NS1 protein activates cells via Toll-like receptor 4 and disrupts endothelial cell monolayer integrity. Sci Transl Med. 2015;7(304): 304ra142.","journal-title":"Sci Transl Med."},{"issue":"7","key":"1116_CR9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005053","volume":"11","author":"J Chen","year":"2015","unstructured":"Chen J, Ng MM, Chu JJ. Activation of TLR2 and TLR6 by dengue NS1 protein and its implications in the immunopathogenesis of dengue virus infection. PLoS Pathog. 2015;11(7): e1005053.","journal-title":"PLoS Pathog"},{"issue":"1","key":"1116_CR10","doi-asserted-by":"publisher","first-page":"142","DOI":"10.4269\/ajtmh.2006.74.142","volume":"74","author":"LC Chen","year":"2006","unstructured":"Chen LC, Lei HY, Liu CC, Shiesh SC, Chen SH, Liu HS, et al. Correlation of serum levels of macrophage migration inhibitory factor with disease severity and clinical outcome in dengue patients. Am J Trop Med Hyg. 2006;74(1):142\u20137.","journal-title":"Am J Trop Med Hyg"},{"issue":"4","key":"1116_CR11","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1078\/0171-2985-00058","volume":"204","author":"EL Azeredo","year":"2001","unstructured":"Azeredo EL, Zagne SM, Santiago MA, Gouvea AS, Santana AA, Neves-Souza PC, et al. Characterisation of lymphocyte response and cytokine patterns in patients with dengue fever. Immunobiology. 2001;204(4):494\u2013507.","journal-title":"Immunobiology"},{"issue":"2","key":"1116_CR12","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1590\/S0074-02761994000200010","volume":"89","author":"G Kuno","year":"1994","unstructured":"Kuno G, Bailey RE. Cytokine responses to dengue infection among Puerto-Rican patients. Mem I Oswaldo Cruz. 1994;89(2):179\u201382.","journal-title":"Mem I Oswaldo Cruz"},{"issue":"2","key":"1116_CR13","first-page":"218","volume":"36","author":"N Iyngkaran","year":"1995","unstructured":"Iyngkaran N, Yadav M, Sinniah M. Augmented inflammatory cytokines in primary dengue infection progressing to shock. Singap Med J. 1995;36(2):218\u201321.","journal-title":"Singap Med J"},{"issue":"1","key":"1116_CR14","doi-asserted-by":"publisher","first-page":"424","DOI":"10.4049\/jimmunol.1100750","volume":"187","author":"P Avirutnan","year":"2011","unstructured":"Avirutnan P, Hauhart RE, Somnuke P, Blom AM, Diamond MS, Atkinson JP. Binding of flavivirus nonstructural protein NS1 to C4b binding protein modulates complement activation. J Immunol. 2011;187(1):424\u201333.","journal-title":"J Immunol"},{"issue":"4","key":"1116_CR15","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1084\/jem.20092545","volume":"207","author":"P Avirutnan","year":"2010","unstructured":"Avirutnan P, Fuchs A, Hauhart RE, Somnuke P, Youn S, Diamond MS, et al. Antagonism of the complement component C4 by flavivirus nonstructural protein NS1. J Exp Med. 2010;207(4):793\u2013806.","journal-title":"J Exp Med"},{"issue":"21","key":"1116_CR16","doi-asserted-by":"publisher","first-page":"9570","DOI":"10.1128\/JVI.00912-16","volume":"90","author":"JN Conde","year":"2016","unstructured":"Conde JN, da Silva EM, Allonso D, Coelho DR, Andrade ID, de Medeiros LN, et al. Inhibition of the membrane attack complex by dengue virus NS1 through interaction with vitronectin and terminal complement proteins. J Virol. 2016;90(21):9570\u201381.","journal-title":"J Virol"},{"issue":"7074","key":"1116_CR17","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1038\/nature04388","volume":"439","author":"M Vignuzzi","year":"2006","unstructured":"Vignuzzi M, Stone JK, Arnold JJ, Cameron CE, Andino R. Quasispecies diversity determines pathogenesis through cooperative interactions in a viral population. Nature. 2006;439(7074):344\u20138.","journal-title":"Nature"},{"issue":"6","key":"1116_CR18","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1089\/vbz.2010.0177","volume":"11","author":"R Rodriguez-Roche","year":"2011","unstructured":"Rodriguez-Roche R, Sanchez L, Burgher Y, Rosario D, Alvarez M, Kouri G, et al. Virus role during intraepidemic increase in dengue disease severity. Vector Borne Zoonotic Dis. 2011;11(6):675\u201381.","journal-title":"Vector Borne Zoonotic Dis"},{"issue":"2","key":"1116_CR19","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.virol.2005.01.037","volume":"334","author":"R Rodriguez-Roche","year":"2005","unstructured":"Rodriguez-Roche R, Alvarez M, Gritsun T, Halstead S, Kouri G, Gould EA, et al. Virus evolution during a severe dengue epidemic in Cuba, 1997. Virology. 2005;334(2):154\u20139.","journal-title":"Virology"},{"issue":"498","key":"1116_CR20","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aat7726","volume":"11","author":"KWK Chan","year":"2019","unstructured":"Chan KWK, Watanabe S, Jin JY, Pompon J, Teng D, Alonso S, et al. A T164S mutation in the dengue virus NS1 protein is associated with greater disease severity in mice. Sci Transl Med. 2019;11(498): eaat7726.","journal-title":"Sci Transl Med"},{"issue":"6","key":"1116_CR21","doi-asserted-by":"publisher","first-page":"107617","DOI":"10.1016\/j.celrep.2020.107617","volume":"31","author":"MM Choy","year":"2020","unstructured":"Choy MM, Ng DHL, Siriphanitchakorn T, Ng WC, Sundstrom KB, Tan HC, et al. A non-structural 1 protein G53D substitution attenuates a clinically tested live dengue vaccine. Cell Rep. 2020;31(6):107617.","journal-title":"Cell Rep"},{"issue":"11","key":"1116_CR22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005277","volume":"11","author":"P Scaturro","year":"2015","unstructured":"Scaturro P, Cortese M, Chatel-Chaix L, Fischl W, Bartenschlager R. Dengue virus non-structural protein 1 modulates infectious particle production via interaction with the structural proteins. PLoS Pathog. 2015;11(11): e1005277.","journal-title":"PLoS Pathog"},{"issue":"1","key":"1116_CR23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0011885","volume":"18","author":"Y Samune","year":"2024","unstructured":"Samune Y, Saito A, Sasaki T, Koketsu R, Srimark N, Phadungsombat J, et al. Genetic regions affecting the replication and pathogenicity of dengue virus type 2. PLoS Negl Trop Dis. 2024;18(1): e0011885.","journal-title":"PLoS Negl Trop Dis"},{"issue":"10","key":"1116_CR24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002934","volume":"8","author":"S Aguirre","year":"2012","unstructured":"Aguirre S, Maestre AM, Pagni S, Patel JR, Savage T, Gutman D, et al. DENV inhibits type I IFN production in infected cells by cleaving human STING. PLoS Pathog. 2012;8(10): e1002934.","journal-title":"PLoS Pathog"},{"issue":"12","key":"1116_CR25","first-page":"1","volume":"5","author":"SF Wang","year":"2016","unstructured":"Wang SF, Chang K, Loh EW, Wang WH, Tseng SP, Lu PL, et al. Consecutive large dengue outbreaks in Taiwan in 2014\u20132015. Emerg Microbes Infect. 2016;5(12):1\u20133.","journal-title":"Emerg Microbes Infect"},{"issue":"3","key":"1116_CR26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003265","volume":"9","author":"J Morrison","year":"2013","unstructured":"Morrison J, Laurent-Rolle M, Maestre AM, Rajsbaum R, Pisanelli G, Simon V, et al. Dengue virus co-opts UBR4 to degrade STAT2 and antagonize type I interferon signaling. PLoS Pathog. 2013;9(3): e1003265.","journal-title":"PLoS Pathog"},{"key":"1116_CR27","doi-asserted-by":"publisher","first-page":"17006","DOI":"10.1038\/celldisc.2017.6","volume":"3","author":"YX Wu","year":"2017","unstructured":"Wu YX, Liu QX, Zhou J, Xie WH, Chen C, Wang ZF, et al. Zika virus evades interferon-mediated antiviral response through the co-operation of multiple nonstructural proteins. Cell Discov. 2017;3:17006.","journal-title":"Cell Discov"},{"issue":"18","key":"1116_CR28","doi-asserted-by":"publisher","first-page":"e02396","DOI":"10.1128\/JVI.02396-16","volume":"91","author":"HL Zhang","year":"2017","unstructured":"Zhang HL, Ye HQ, Liu SQ, Deng CL, Li XD, Shi PY, et al. West Nile virus NS1 antagonizes interferon beta production by targeting RIG-I and MDA5. J Virol. 2017;91(18):e02396-e2416.","journal-title":"J Virol"},{"key":"1116_CR29","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.ijid.2019.09.007","volume":"88","author":"WH Wang","year":"2019","unstructured":"Wang WH, Lin CY, Chang K, Urbina AN, Assavalapsakul W, Thitithanyanont A, et al. A clinical and epidemiological survey of the largest dengue outbreak in Southern Taiwan in 2015. Int J Infect Dis. 2019;88:88\u201399.","journal-title":"Int J Infect Dis"},{"key":"1116_CR30","doi-asserted-by":"publisher","first-page":"894200","DOI":"10.3389\/fmicb.2022.894200","volume":"13","author":"D Cheng","year":"2022","unstructured":"Cheng D, Huang SW, Chin WX, Hung SJ, Tsai HP, Chu JJH, et al. Impact of intrahost NS5 nucleotide variations on dengue virus replication. Front Microbiol. 2022;13:894200.","journal-title":"Front Microbiol"},{"issue":"6","key":"1116_CR31","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0012268","volume":"18","author":"YY Tsai","year":"2024","unstructured":"Tsai YY, Cheng D, Huang SW, Hung SJ, Wang YF, Lin YJ, et al. The molecular epidemiology of a dengue virus outbreak in Taiwan: population wide versus infrapopulation mutation analysis. PLoS Negl Trop Dis. 2024;18(6): e0012268.","journal-title":"PLoS Negl Trop Dis"},{"issue":"2","key":"1116_CR32","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/j.antiviral.2013.03.008","volume":"98","author":"DA Muller","year":"2013","unstructured":"Muller DA, Young PR. The flavivirus NS1 protein: molecular and structural biology, immunology, role in pathogenesis and application as a diagnostic biomarker. Antiviral Res. 2013;98(2):192\u2013208.","journal-title":"Antiviral Res"},{"issue":"2","key":"1116_CR33","doi-asserted-by":"publisher","first-page":"1644","DOI":"10.3390\/cimb45020106","volume":"45","author":"E Ogire","year":"2023","unstructured":"Ogire E, El-Kalamouni C, Despr\u00e8s P, Roche M. Stability of dengue 2 nonstructural glycoprotein 1 (NS1) is affected by the nature of basic residue at position NS1-324. Curr Issues Mol Biol. 2023;45(2):1644\u201354.","journal-title":"Curr Issues Mol Biol"},{"issue":"1","key":"1116_CR34","doi-asserted-by":"publisher","first-page":"13105","DOI":"10.1038\/s41598-023-40463-4","volume":"13","author":"Y Kawasaki","year":"2023","unstructured":"Kawasaki Y, Abe H, Yasuda J. Comparison of genome replication fidelity between SARS-CoV-2 and influenza A virus in cell culture. Sci Rep. 2023;13(1):13105.","journal-title":"Sci Rep"},{"issue":"1","key":"1116_CR35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12985-020-1280-z","volume":"17","author":"TT Dang","year":"2020","unstructured":"Dang TT, Ha Pham M, Bui HV, Le DV. Whole genome sequencing and genetic variations in several dengue virus type 1 strains from unusual dengue epidemic of 2017 in Vietnam. Virol J. 2020;17(1):1\u201310.","journal-title":"Virol J"},{"issue":"5","key":"1116_CR36","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1016\/j.celrep.2018.10.006","volume":"25","author":"EN Gallichotte","year":"2018","unstructured":"Gallichotte EN, Baric TJ, Nivarthi U, Delacruz MJ, Graham R, Widman DG, et al. Genetic variation between dengue virus type 4 strains impacts human antibody binding and neutralization. Cell Rep. 2018;25(5):1214\u201324.","journal-title":"Cell Rep"},{"issue":"1","key":"1116_CR37","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1038\/s41467-017-02816-2","volume":"9","author":"H Xia","year":"2018","unstructured":"Xia H, Luo H, Shan C, Muruato AE, Nunes BTD, Medeiros DBA, et al. An evolutionary NS1 mutation enhances Zika virus evasion of host interferon induction. Nat Commun. 2018;9(1):414.","journal-title":"Nat Commun"},{"issue":"5","key":"1116_CR38","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1038\/icb.2017.5","volume":"95","author":"N Modhiran","year":"2017","unstructured":"Modhiran N, Watterson D, Blumenthal A, Baxter AG, Young PR, Stacey KJ. Dengue virus NS1 protein activates immune cells via TLR4 but not TLR2 or TLR6. Immunol Cell Biol. 2017;95(5):491\u20135.","journal-title":"Immunol Cell Biol"},{"issue":"3","key":"1116_CR39","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011241","volume":"19","author":"YS Kao","year":"2023","unstructured":"Kao YS, Wang LC, Chang PC, Lin HM, Lin YS, Yu CY, et al. Negative regulation of type I interferon signaling by integrin-linked kinase permits dengue virus replication. PLoS Pathog. 2023;19(3): e1011241.","journal-title":"PLoS Pathog"},{"issue":"1\u20132","key":"1116_CR40","doi-asserted-by":"publisher","first-page":"71","DOI":"10.4269\/ajtmh.2000.63.71","volume":"63","author":"YH Huang","year":"2000","unstructured":"Huang YH, Lei HY, Liu HS, Lin YS, Liu CC, Yeh TM. Dengue virus infects human endothelial cells and induces IL-6 and IL-8 production. Am J Trop Med Hyg. 2000;63(1\u20132):71\u20135.","journal-title":"Am J Trop Med Hyg"},{"issue":"1","key":"1116_CR41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008709","volume":"5","author":"D Priyadarshini","year":"2010","unstructured":"Priyadarshini D, Gadia RR, Tripathy A, Gurukumar KR, Bhagat A, Patwardhan S, et al. Clinical findings and pro-inflammatory cytokines in dengue patients in Western India: a facility-based study. PLoS ONE. 2010;5(1): e8709.","journal-title":"PLoS ONE"},{"issue":"5","key":"1116_CR42","doi-asserted-by":"publisher","first-page":"943","DOI":"10.4269\/ajtmh.19-0487","volume":"102","author":"HA Imad","year":"2020","unstructured":"Imad HA, Phumratanaprapin W, Phonrat B, Chotivanich K, Charunwatthana P, Muangnoicharoen S, et al. Cytokine expression in dengue fever and dengue hemorrhagic fever patients with bleeding and severe hepatitis. Am J Trop Med Hyg. 2020;102(5):943\u201350.","journal-title":"Am J Trop Med Hyg"},{"issue":"6","key":"1116_CR43","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/j.cyto.2004.05.007","volume":"27","author":"ML Avila-Aguero","year":"2004","unstructured":"Avila-Aguero ML, Avila-Aguero CR, Um SL, Soriano-Fallas A, Canas-Coto A, Yan SB. Systemic host inflammatory and coagulation response in the Dengue virus primo-infection. Cytokine. 2004;27(6):173\u20139.","journal-title":"Cytokine"},{"key":"1116_CR44","doi-asserted-by":"publisher","first-page":"199306","DOI":"10.1016\/j.virusres.2023.199306","volume":"341","author":"P Bhatt","year":"2024","unstructured":"Bhatt P, Varma M, Sood V, Ambikan A, Jayaram A, Babu N, et al. Temporal cytokine storm dynamics in dengue infection predicts severity. Virus Res. 2024;341:199306.","journal-title":"Virus Res"}],"container-title":["Journal of Biomedical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12929-024-01116-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12929-024-01116-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12929-024-01116-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T00:01:47Z","timestamp":1740009707000},"score":1,"resource":{"primary":{"URL":"https:\/\/jbiomedsci.biomedcentral.com\/articles\/10.1186\/s12929-024-01116-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,20]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["1116"],"URL":"https:\/\/doi.org\/10.1186\/s12929-024-01116-4","relation":{},"ISSN":["1423-0127"],"issn-type":[{"value":"1423-0127","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,20]]},"assertion":[{"value":"15 September 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 December 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 February 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"25"}}