{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T04:50:35Z","timestamp":1778647835576,"version":"3.51.4"},"reference-count":82,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,17]],"date-time":"2021-07-17T00:00:00Z","timestamp":1626480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011057","name":"National Center for Genetic Engineering and Biotechnology","doi-asserted-by":"publisher","award":["P17-51096"],"award-info":[{"award-number":["P17-51096"]}],"id":[{"id":"10.13039\/501100011057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004396","name":"Thailand Research Fund","doi-asserted-by":"publisher","award":["RSA6080001"],"award-info":[{"award-number":["RSA6080001"]}],"id":[{"id":"10.13039\/501100004396","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Dengue virus (DENV) infection causes a spectrum of dengue diseases that have unclear underlying mechanisms. Nonstructural protein 1 (NS1) is a multifunctional protein of DENV that is involved in DENV infection and dengue pathogenesis. This study investigated the potential post-translational modification of DENV NS1 by phosphorylation following DENV infection. Using liquid chromatography-tandem mass spectrometry (LC-MS\/MS), 24 potential phosphorylation sites were identified in both cell-associated and extracellular NS1 proteins from three different cell lines infected with DENV. Cell-free kinase assays also demonstrated kinase activity in purified preparations of DENV NS1 proteins. Further studies were conducted to determine the roles of specific phosphorylation sites on NS1 proteins by site-directed mutagenesis with alanine substitution. The T27A and Y32A mutations had a deleterious effect on DENV infectivity. The T29A, T230A, and S233A mutations significantly decreased the production of infectious DENV but did not affect relative levels of intracellular DENV NS1 expression or NS1 secretion. Only the T230A mutation led to a significant reduction of detectable DENV NS1 dimers in virus-infected cells; however, none of the mutations interfered with DENV NS1 oligomeric formation. These findings highlight the importance of DENV NS1 phosphorylation that may pave the way for future target-specific antiviral drug design.<\/jats:p>","DOI":"10.3390\/v13071393","type":"journal-article","created":{"date-parts":[[2021,7,18]],"date-time":"2021-07-18T21:18:52Z","timestamp":1626643132000},"page":"1393","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Potential Phosphorylation of Viral Nonstructural Protein 1 in Dengue Virus Infection"],"prefix":"10.3390","volume":"13","author":[{"given":"Thanyaporn","family":"Dechtawewat","sequence":"first","affiliation":[{"name":"Division of Molecular Medicine, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3696-8390","authenticated-orcid":false,"given":"Sittiruk","family":"Roytrakul","sequence":"additional","affiliation":[{"name":"Functional Proteomics Technology Laboratory, Functional Ingredients and Food Innovation Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Bangkok 12120, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yodying","family":"Yingchutrakul","sequence":"additional","affiliation":[{"name":"Functional Proteomics Technology Laboratory, Functional Ingredients and Food Innovation Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Bangkok 12120, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sawanya","family":"Charoenlappanit","sequence":"additional","affiliation":[{"name":"Functional Proteomics Technology Laboratory, Functional Ingredients and Food Innovation Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Bangkok 12120, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bunpote","family":"Siridechadilok","sequence":"additional","affiliation":[{"name":"Molecular Biology of Dengue and Flaviviruses Research Team, Medical Molecular Biotechnology Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Bangkok 10700, Thailand"},{"name":"Division of Dengue Hemorrhagic Fever Research, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5270-493X","authenticated-orcid":false,"given":"Thawornchai","family":"Limjindaporn","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arunothai","family":"Mangkang","sequence":"additional","affiliation":[{"name":"Molecular Biology of Dengue and Flaviviruses Research Team, Medical Molecular Biotechnology Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Bangkok 10700, Thailand"},{"name":"Division of Dengue Hemorrhagic Fever Research, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1967-2670","authenticated-orcid":false,"given":"Tanapan","family":"Prommool","sequence":"additional","affiliation":[{"name":"Molecular Biology of Dengue and Flaviviruses Research Team, Medical Molecular Biotechnology Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Bangkok 10700, Thailand"},{"name":"Division of Dengue Hemorrhagic Fever Research, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"},{"name":"Siriraj Center of Research Excellence in Dengue and Emerging Pathogens, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunya","family":"Puttikhunt","sequence":"additional","affiliation":[{"name":"Molecular Biology of Dengue and Flaviviruses Research Team, Medical Molecular Biotechnology Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Bangkok 10700, Thailand"},{"name":"Division of Dengue Hemorrhagic Fever Research, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"},{"name":"Siriraj Center of Research Excellence in Dengue and Emerging Pathogens, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pucharee","family":"Songprakhon","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5937-7254","authenticated-orcid":false,"given":"Kessiri","family":"Kongmanas","sequence":"additional","affiliation":[{"name":"Division of Dengue Hemorrhagic Fever Research, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"},{"name":"Siriraj Center of Research Excellence in Dengue and Emerging Pathogens, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nuttapong","family":"Kaewjew","sequence":"additional","affiliation":[{"name":"Division of Dengue Hemorrhagic Fever Research, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"},{"name":"Siriraj Center of Research Excellence in Dengue and Emerging Pathogens, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0053-3045","authenticated-orcid":false,"given":"Panisadee","family":"Avirutnan","sequence":"additional","affiliation":[{"name":"Division of Dengue Hemorrhagic Fever Research, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"},{"name":"Siriraj Center of Research Excellence in Dengue and Emerging Pathogens, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9779-5927","authenticated-orcid":false,"given":"Pa-thai","family":"Yenchitsomanus","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prida","family":"Malasit","sequence":"additional","affiliation":[{"name":"Molecular Biology of Dengue and Flaviviruses Research Team, Medical Molecular Biotechnology Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Bangkok 10700, Thailand"},{"name":"Division of Dengue Hemorrhagic Fever Research, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"},{"name":"Siriraj Center of Research Excellence in Dengue and Emerging Pathogens, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9336-3331","authenticated-orcid":false,"given":"Sansanee","family":"Noisakran","sequence":"additional","affiliation":[{"name":"Molecular Biology of Dengue and Flaviviruses Research Team, Medical Molecular Biotechnology Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Bangkok 10700, Thailand"},{"name":"Division of Dengue Hemorrhagic Fever Research, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"},{"name":"Siriraj Center of Research Excellence in Dengue and Emerging Pathogens, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","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":"ref_2","unstructured":"(2021, June 01). WHO Dengue and Severe Dengue. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/dengue-and-severe-dengue."},{"key":"ref_3","unstructured":"World Health Organization (2009). Dengue Guidelines for Diagnosis, Treatment, Prevention and Control: New Edition, World Health Organization."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1056\/NEJMoa1800820","article-title":"Effect of Dengue Serostatus on Dengue Vaccine Safety and Efficacy","volume":"379","author":"Sridhar","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Da Silveira, L.T.C., Tura, B., and Santos, M. (2019). Systematic review of dengue vaccine efficacy. BMC Infect. Dis., 19.","DOI":"10.1186\/s12879-019-4369-5"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.3389\/fimmu.2020.01252","article-title":"Anti-dengue Vaccines: From Development to Clinical Trials","volume":"11","author":"Souza","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.coviro.2020.09.004","article-title":"Dengue vaccine development by the year 2020: Challenges and prospects","volume":"43","year":"2020","journal-title":"Curr. Opin. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Lopez-Medina, E., Biswal, S., Saez-Llorens, X., Borja-Tabora, C., Bravo, L., Sirivichayakul, C., Vargas, L.M., Alera, M.T., Velasquez, H., and Reynales, H. (2020). Efficacy of a dengue vaccine candidate (TAK-003) in healthy children and adolescents two years after vaccination. J. Infect. Dis., jiaa761.","DOI":"10.1093\/infdis\/jiaa761"},{"key":"ref_9","unstructured":"Knipe, D.M., Howley, P.M., Griffin, D.E., Lamb, R.A., Martin, M.A., Roizman, B., and Strauss, S.E. (2001). Flaviviridae: The viruses and their replication. Fields Virology, Lippincott Williams & Wilkins. [4th ed.]."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.mib.2008.06.004","article-title":"Structural proteomics of dengue virus","volume":"11","author":"Perera","year":"2008","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1128\/JCM.40.02.376-381.2002","article-title":"Enzyme-Linked Immunosorbent Assay Specific to Dengue Virus Type 1 Nonstructural Protein NS1 Reveals Circulation of the Antigen in the Blood during the Acute Phase of Disease in Patients Experiencing Primary or Secondary Infections","volume":"40","author":"Alcon","year":"2002","journal-title":"J. Clin. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1128\/JCM.38.3.1053-1057.2000","article-title":"An antigen capture enzyme-linked immunosorbent assay reveals high levels of the dengue virus protein NS1 in the sera of infected patients","volume":"38","author":"Young","year":"2000","journal-title":"J. Clin. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1086\/343813","article-title":"High Circulating Levels of the Dengue Virus Nonstructural Protein NS1 Early in Dengue Illness Correlate with the Development of Dengue Hemorrhagic Fever","volume":"186","author":"Libraty","year":"2002","journal-title":"J. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1096\/fj.99-0829com","article-title":"Dengue virus nonstructural protein 1 is expressed in a glycosyl-phosphatidylinositol-linked form that is capable of signal transduction","volume":"14","author":"Jacobs","year":"2000","journal-title":"FASEB J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/0042-6822(89)90544-8","article-title":"Newly synthesized dengue-2 virus nonstructural protein NS1 is a soluble protein but becomes partially hydrophobic and membrane-associated after dimerization","volume":"171","author":"Winkler","year":"1989","journal-title":"Virology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/0042-6822(88)90408-4","article-title":"Evidence that the mature form of the flavivirus nonstructural protein NS1 is a dimer","volume":"162","author":"Winkler","year":"1988","journal-title":"Virology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.1099\/vir.0.83620-0","article-title":"Association of dengue virus NS1 protein with lipid rafts","volume":"89","author":"Noisakran","year":"2008","journal-title":"J. Gen. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jviromet.2007.01.008","article-title":"Characterization of dengue virus NS1 stably expressed in 293T cell lines","volume":"142","author":"Noisakran","year":"2007","journal-title":"J. Virol. Methods"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6104","DOI":"10.1128\/JVI.73.7.6104-6110.1999","article-title":"Dengue virus type 1 nonstructural glycoprotein NS1 is secreted from mammalian cells as a soluble hexamer in a glycosylation-dependent fashion","volume":"73","author":"Flamand","year":"1999","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8003","DOI":"10.1073\/pnas.1017338108","article-title":"Secreted dengue virus nonstructural protein NS1 is an atypical barrel-shaped high-density lipoprotein","volume":"108","author":"Gutsche","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Avirutnan, P., Zhang, L., Punyadee, N., Manuyakorn, A., Puttikhunt, C., Kasinrerk, W., Malasit, P., Atkinson, J.P., and Diamond, M.S. (2007). Secreted NS1 of dengue virus attaches to the surface of cells via interactions with heparan sulfate and chondroitin sulfate E. PLoS Pathog., 3.","DOI":"10.1371\/journal.ppat.0030183"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6650","DOI":"10.1128\/jvi.71.9.6650-6661.1997","article-title":"Ultrastructure of Kunjin virus-infected cells: Colocalization of NS1 and NS3 with double-stranded RNA, and of NS2B with NS3, in virus-induced membrane structures","volume":"71","author":"Westaway","year":"1997","journal-title":"J. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1006\/viro.1996.0307","article-title":"Immunolocalization of the Dengue Virus Nonstructural Glycoprotein NS1 Suggests a Role in Viral RNA Replication","volume":"220","author":"Mackenzie","year":"1996","journal-title":"Virology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.chom.2009.03.007","article-title":"Composition and Three-Dimensional Architecture of the Dengue Virus Replication and Assembly Sites","volume":"5","author":"Welsch","year":"2009","journal-title":"Cell Host Microbe"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"P\u0142aszczyca, A., Scaturro, P., Neufeldt, C.J., Cortese, M., Cerikan, B., Ferla, S., Brancale, A., Pichlmair, A., and Bartenschlager, R. (2019). A novel interaction between dengue virus nonstructural protein 1 and the NS4A-2K-4B precursor is required for viral RNA replication but not for formation of the membranous replication organelle. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007736"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9608","DOI":"10.1128\/jvi.71.12.9608-9617.1997","article-title":"trans-Complementation of yellow fever virus NS1 reveals a role in early RNA replication","volume":"71","author":"Lindenbach","year":"1997","journal-title":"J. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1186\/1743-422X-10-339","article-title":"Non-structural protein-1 is required for West Nile virus replication complex formation and viral RNA synthesis","volume":"10","author":"Youn","year":"2013","journal-title":"Virol. J."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Scaturro, P., Cortese, M., Chatel-Chaix, L., Fischl, W., and Bartenschlager, R. (2015). Dengue Virus Non-structural Protein 1 Modulates Infectious Particle Production via Interaction with the Structural Proteins. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1005277"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"11403","DOI":"10.1128\/JVI.79.17.11403-11411.2005","article-title":"The Secreted Form of Dengue Virus Nonstructural Protein NS1 Is Endocytosed by Hepatocytes and Accumulates in Late Endosomes: Implications for Viral Infectivity","volume":"79","author":"Drouet","year":"2005","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.virol.2016.06.008","article-title":"Dengue virus NS1 enhances viral replication and pro-inflammatory cytokine production in human dendritic cells","volume":"496","author":"Alayli","year":"2016","journal-title":"Virology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1084\/jem.20092545","article-title":"Antagonism of the complement component C4 by flavivirus nonstructural protein NS1","volume":"207","author":"Avirutnan","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"424","DOI":"10.4049\/jimmunol.1100750","article-title":"Binding of Flavivirus Nonstructural Protein NS1 to C4b Binding Protein Modulates Complement Activation","volume":"187","author":"Avirutnan","year":"2011","journal-title":"J. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4053","DOI":"10.4049\/jimmunol.1600323","article-title":"Secreted NS1 Protects Dengue Virus from Mannose-Binding Lectin-Mediated Neutralization","volume":"197","author":"Thiemmeca","year":"2016","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Chen, J., Ng, M.M., and Chu, J.J. (2015). Activation of TLR2 and TLR6 by Dengue NS1 Protein and Its Implications in the Immuno-pathogenesis of Dengue Virus Infection. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1005053"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"304ra142","DOI":"10.1126\/scitranslmed.aaa3863","article-title":"Dengue virus NS1 protein activates cells via Toll-like receptor 4 and disrupts endothelial cell monolayer integrity","volume":"7","author":"Modhiran","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"304ra141","DOI":"10.1126\/scitranslmed.aaa3787","article-title":"Dengue virus NS1 triggers endothelial permeability and vascular leak that is prevented by NS1 vaccination","volume":"7","author":"Beatty","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.4049\/jimmunol.105.6.1565","article-title":"Partial purification and characterization of a dengue virus soluble complement-fixing antigen","volume":"105","author":"Brandt","year":"1970","journal-title":"J. Immunol."},{"key":"ref_38","first-page":"46","article-title":"Circulating immune complexes in serum from patients with dengue haemorrhagic fever","volume":"36","author":"Ruangjirachuporn","year":"1979","journal-title":"Clin. Exp. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1086\/500949","article-title":"Vascular Leakage in Severe Dengue Virus Infections: A Potential Role for the Nonstructural Viral Protein NS1 and Complement","volume":"193","author":"Avirutnan","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1099\/jgv.0.001401","article-title":"Dengue virus non-structural protein 1 activates the p38 MAPK pathway to decrease barrier integrity in primary human endothelial cells","volume":"101","author":"Endy","year":"2020","journal-title":"J. Gen. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"270","DOI":"10.3389\/fgene.2014.00270","article-title":"Physicochemical mechanisms of protein regulation by phosphorylation","volume":"5","author":"Nishi","year":"2014","journal-title":"Front. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/S0968-0004(00)01712-6","article-title":"The regulation of protein function by multisite phosphorylation\u2014A 25 year update","volume":"25","author":"Cohen","year":"2000","journal-title":"Trends Biochem. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1038\/nrm2203","article-title":"Mechanisms of specificity in protein phosphorylation","volume":"8","author":"Ubersax","year":"2007","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.virol.2009.10.019","article-title":"JNK phosphorylation, induced during dengue virus infection, is important for viral infection and requires the presence of cholesterol","volume":"396","author":"Medina","year":"2010","journal-title":"Virology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1160\/TH07-08-0483","article-title":"Crosstalk between coagulation and inflammation during Dengue virus infection","volume":"99","author":"Castillo","year":"2008","journal-title":"Thromb. Haemost."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1007\/s00705-011-0969-0","article-title":"The dengue virus nonstructural protein 1 (NS1) increases NF-\u03baB transcriptional activity in HepG2 cells","volume":"156","author":"Silva","year":"2011","journal-title":"Arch. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/j.bbrc.2007.08.137","article-title":"Secreted complement regulatory protein clusterin interacts with dengue virus nonstructural protein 1","volume":"362","author":"Kurosu","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.virusres.2005.03.025","article-title":"Recombinant non-structural 1 (NS1) protein of dengue-2 virus interacts with human STAT3\u03b2 protein","volume":"112","author":"Chua","year":"2005","journal-title":"Virus Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"012187","DOI":"10.1074\/mcp.M111.012187","article-title":"A Physical Interaction Network of Dengue Virus and Human Proteins","volume":"10","author":"Khadka","year":"2011","journal-title":"Mol. Cell. Proteom."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Silva, E.M., Conde, J.N., Allonso, D., Nogueira, M.L., and Mohana-Borges, R. (2013). Mapping the Interactions of Dengue Virus NS1 Protein with Human Liver Proteins Using a Yeast Two-Hybrid System: Identification of C1q as an Interacting Partner. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0057514"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"11871","DOI":"10.1128\/JVI.01342-15","article-title":"Dengue virus NS1 protein modulates cellular energy metabolism by increasing glyceraldehyde-3-phosphate dehydrogenase activity","volume":"89","author":"Allonso","year":"2015","journal-title":"J. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.virol.2015.05.017","article-title":"Dengue virus NS1 protein interacts with the ribosomal protein RPL18: This interaction is required for viral translation and replication in Huh-7 cells","volume":"484","author":"Ludert","year":"2015","journal-title":"Virology"},{"key":"ref_53","first-page":"12701270","article-title":"Mass spectrometric analysis of host cell proteins interacting with dengue virus nonstructural protein 1 in dengue virus-infected HepG2 cells","volume":"1864","author":"Dechtawewat","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1016\/j.celrep.2018.01.038","article-title":"A Global Interactome Map of the Dengue Virus NS1 Identifies Virus Restriction and Dependency Host Factors","volume":"22","author":"Hafirassou","year":"2018","journal-title":"Cell Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1099\/jgv.0.001134","article-title":"Human glucose-regulated protein 78 modulates intracellular production and secretion of nonstructural protein 1 of dengue virus","volume":"99","author":"Songprakhon","year":"2018","journal-title":"J. Gen. Virol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Suphatrakul, A., Duangchinda, T., Jupatanakul, N., Prasittisa, K., Onnome, S., Pengon, J., and Siridechadilok, B. (2018). Multi-color flu-orescent reporter dengue viruses with improved stability for analysis of a multi-virus infection. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0194399"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0166-0934(03)00045-4","article-title":"Production of anti-dengue NS1 monoclonal antibodies by DNA immunization","volume":"109","author":"Puttikhunt","year":"2003","journal-title":"J. Virol. Methods"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"162","DOI":"10.4269\/ajtmh.1985.34.162","article-title":"Epitopic Analysis of Antigenic Determinants on the Surface of Dengue-2 Virions Using Monoclonal Antibodies","volume":"34","author":"Henchal","year":"1985","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"830","DOI":"10.4269\/ajtmh.1982.31.830","article-title":"Dengue virus-specific and flavivirus group determinants identified with monoclonal antibodies by indirect immunofluorescence","volume":"31","author":"Henchal","year":"1982","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e9988","DOI":"10.7717\/peerj.9988","article-title":"Analysis of the infant gut microbiome reveals metabolic functional roles as-sociated with healthy infants and infants with atopic dermatitis using metaproteomics","volume":"8","author":"Kingkaw","year":"2020","journal-title":"PeerJ"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3551","DOI":"10.1002\/(SICI)1522-2683(19991201)20:18<3551::AID-ELPS3551>3.0.CO;2-2","article-title":"Probability-based protein identification by searching sequence databases using mass spectrometry data","volume":"20","author":"Perkins","year":"1999","journal-title":"Electrophoresis"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"12667","DOI":"10.1128\/JVI.02261-13","article-title":"A Simplified Positive-Sense-RNA Virus Construction Approach That Enhances Analysis Throughput","volume":"87","author":"Siridechadilok","year":"2013","journal-title":"J. Virol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s12985-014-0219-7","article-title":"Role of human heterogeneous nuclear ribonucleoprotein C1\/C2 in dengue virus replication","volume":"12","author":"Dechtawewat","year":"2015","journal-title":"Virol. J."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Kongmanas, K., Punyadee, N., Wasuworawong, K., Songjaeng, A., Prommool, T., Pewkliang, Y., Manocheewa, S., Thiemmeca, S., Sa-Ngiamsuntorn, K., and Puttikhunt, C. (2020). Immortalized stem cell-derived hepatocyte-like cells: An alternative model for studying dengue pathogenesis and therapy. PLoS Negl. Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0008835"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1002\/jcp.24728","article-title":"Proteomic Characterization of Pig Sperm Anterior Head Plasma Membrane Reveals Roles of Acrosomal Proteins in ZP3 Binding","volume":"230","author":"Kongmanas","year":"2015","journal-title":"J. Cell. Physiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1099\/vir.0.039321-0","article-title":"Structure of the dengue virus glycoprotein non-structural protein 1 by electron microscopy and single-particle analysis","volume":"93","author":"Muller","year":"2012","journal-title":"J. Gen. Virol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.virol.2011.02.022","article-title":"N-linked glycosylation of dengue virus NS1 protein modulates secretion, cell-surface expression, hexamer stability, and interactions with human complement","volume":"413","author":"Somnuke","year":"2011","journal-title":"Virology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"5257","DOI":"10.3390\/v7102872","article-title":"Phosphorylation of Single Stranded RNA Virus Proteins and Potential for Novel Therapeutic Strategies","volume":"7","author":"Keck","year":"2015","journal-title":"Viruses"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1002\/rmv.722","article-title":"Phosphorylation events during viral infections provide potential therapeutic targets","volume":"22","author":"Keating","year":"2012","journal-title":"Rev. Med. Virol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1128\/JVI.01369-10","article-title":"Viral Serine\/Threonine Protein Kinases","volume":"85","author":"Jacob","year":"2010","journal-title":"J. Virol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"19100","DOI":"10.1074\/jbc.270.32.19100","article-title":"Association between NS3 and NS5 Proteins of Dengue Virus Type 2 in the Putative RNA Replicase Is Linked to Differential Phosphorylation of NS5","volume":"270","author":"Kapoor","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0168-1702(96)01433-5","article-title":"Phosphorylation of tick-borne encephalitis virus NS5 protein","volume":"49","author":"Morozova","year":"1997","journal-title":"Virus Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"6199","DOI":"10.1128\/JVI.72.7.6199-6206.1998","article-title":"The NS5A\/NS5 proteins of viruses from three genera of the family flaviviridae are phosphorylated by associated serine\/threonine kinases","volume":"72","author":"Reed","year":"1998","journal-title":"J. Virol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"9195","DOI":"10.1128\/JVI.00271-09","article-title":"Protein kinase G phosphorylates mosquito-borne flavivirus NS5","volume":"83","author":"Bhattacharya","year":"2009","journal-title":"J. Virol."},{"key":"ref_75","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":"Ashour","year":"2009","journal-title":"J. Virol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1086\/605847","article-title":"Dengue Virus NS5 Inhibits Interferon-\u03b1 Signaling by Blocking Signal Transducer and Activator of Transcription 2 Phosphorylation","volume":"200","author":"Mazzon","year":"2009","journal-title":"J. Infect. Dis."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"El Sahili, A., and Lescar, J. (2017). Dengue Virus Non-Structural Protein 5. Viruses, 9.","DOI":"10.3390\/v9040091"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1126\/science.1247749","article-title":"Flavivirus NS1 Structures Reveal Surfaces for Associations with Membranes and the Immune System","volume":"343","author":"Akey","year":"2014","journal-title":"Science"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1002\/bies.201400182","article-title":"Structure-guided insights on the role of NS1 in flavivirus infection","volume":"37","author":"Akey","year":"2015","journal-title":"BioEssays"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"11506","DOI":"10.1074\/jbc.M110.154526","article-title":"Differential G-protein-coupled Receptor Phosphorylation Provides Evidence for a Signaling Bar Code","volume":"286","author":"Butcher","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.tips.2008.05.006","article-title":"Location, location, location\u2026site-specific GPCR phosphorylation offers a mechanism for cell-type-specific signalling","volume":"29","author":"Tobin","year":"2008","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1083\/jcb.200610018","article-title":"Phosphorylation and regulation of a G protein-coupled receptor by protein kinase CK2","volume":"177","author":"Torrecilla","year":"2007","journal-title":"J. Cell Biol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/7\/1393\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:31:18Z","timestamp":1760164278000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/7\/1393"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,17]]},"references-count":82,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["v13071393"],"URL":"https:\/\/doi.org\/10.3390\/v13071393","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,17]]}}}