{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T12:38:19Z","timestamp":1776515899075,"version":"3.51.2"},"reference-count":42,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health\/National Institute of Allergy and Infectious Diseases","award":["R01AI099385"],"award-info":[{"award-number":["R01AI099385"]}]},{"name":"National Institute of Health\/National Institute of Allergy and Infectious Diseases","award":["U19AI057266"],"award-info":[{"award-number":["U19AI057266"]}]},{"name":"National Institute of Health\/National Institute of Allergy and Infectious Diseases","award":["D003917"],"award-info":[{"award-number":["D003917"]}]},{"name":"Siriraj Foundation","award":["R01AI099385"],"award-info":[{"award-number":["R01AI099385"]}]},{"name":"Siriraj Foundation","award":["U19AI057266"],"award-info":[{"award-number":["U19AI057266"]}]},{"name":"Siriraj Foundation","award":["D003917"],"award-info":[{"award-number":["D003917"]}]},{"name":"Faculty of Medicine Siriraj Hospital, Mahidol University","award":["R01AI099385"],"award-info":[{"award-number":["R01AI099385"]}]},{"name":"Faculty of Medicine Siriraj Hospital, Mahidol University","award":["U19AI057266"],"award-info":[{"award-number":["U19AI057266"]}]},{"name":"Faculty of Medicine Siriraj Hospital, Mahidol University","award":["D003917"],"award-info":[{"award-number":["D003917"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Little is known about the regulation of B cell subpopulations in association with programmed cell death during dengue virus (DENV) infection. Therefore, blood samples from dengue-infected patients and healthy donors were obtained for B cell subset characterization and the analysis of pro-apoptotic CD95 expression in these cell subsets. The results showed that the activated memory (AM) subset in the patients remained unchanged compared to the healthy donors. In contrast, tissue memory (TM) and antibody-secreting cells (ASCs) were notably increased, whereas na\u00efve cells and resting memory (RM) cells were considerably decreased. Although the ASCs maintained comparably high levels of CD95 expression in both groups, significantly increased percentages of CD95-expressing cells in the other B cell subsets were found in the patients. When B cells from the healthy donors were treated with DENV non-structural protein 1 (NS1), the results showed that the NS1 protein at 2 \u00b5g\/mL could induce CD95 expression and the exposure of phosphatidylserine on the cell membrane in most B cell subsets, except for the RM. This study demonstrates that DENV infection could induce CD95 expression in both activated and resting B cell subsets in all patients. The results also suggest a potential mechanism of apoptotic regulation in B cell subsets through the increased CD95 expression caused by the interaction between the B cells and the NS1 protein.<\/jats:p>","DOI":"10.3390\/v17040541","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T07:49:02Z","timestamp":1744184942000},"page":"541","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dengue Viral Infection Induces Alteration of CD95 Expression in B Cell Subsets with Potential Involvement of Dengue Viral Non-Structural Protein 1"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5523-1631","authenticated-orcid":false,"given":"Siyu","family":"Wang","sequence":"first","affiliation":[{"name":"Graduate Program in Immunology, Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1853-4073","authenticated-orcid":false,"given":"Premrutai","family":"Thitilertdecha","sequence":"additional","affiliation":[{"name":"Siriraj Research Group in Immunobiology and Therapeutic Sciences, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"},{"name":"Biomedical Research Incubator Unit, Research Group and Research Network Division, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1585-495X","authenticated-orcid":false,"given":"Ladawan","family":"Khowawisetsut","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3792-3805","authenticated-orcid":false,"given":"Theeraporn","family":"Maneesawat","sequence":"additional","affiliation":[{"name":"Siriraj Research Group in Immunobiology and Therapeutic Sciences, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"},{"name":"Biomedical Research Incubator Unit, Research Group and Research Network Division, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ampaiwan","family":"Chuansumrit","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0140-4600","authenticated-orcid":false,"given":"Kulkanya","family":"Chokephaibulkit","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1037-6610","authenticated-orcid":false,"given":"Kovit","family":"Pattanapanyasat","sequence":"additional","affiliation":[{"name":"Biomedical Research Incubator Unit, Research Group and Research Network Division, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8784-3005","authenticated-orcid":false,"given":"Nattawat","family":"Onlamoon","sequence":"additional","affiliation":[{"name":"Siriraj Research Group in Immunobiology and Therapeutic Sciences, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"},{"name":"Biomedical Research Incubator Unit, Research Group and Research Network Division, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,8]]},"reference":[{"key":"ref_1","unstructured":"WHO (2025, January 02). Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control. Available online: https:\/\/www.who.int\/publications\/i\/item\/9789241547871."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1007\/s12250-020-00213-6","article-title":"Cutaneous dengue virus inoculation triggers strong B cell reactions but contrastingly poor T Cell responses","volume":"35","year":"2020","journal-title":"Virol. Sin."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Silveira, G.F., Wowk, P.F., Cataneo, A.H.D., Dos Santos, P.F., Delgobo, M., Stimamiglio, M.A., Lo Sarzi, M., Thomazelli, A., Conchon-Costa, I., and Pavanelli, W.R. (2018). Human T lymphocytes are permissive for dengue virus replication. J. Virol., 92.","DOI":"10.1128\/JVI.02181-17"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.immuni.2016.09.001","article-title":"Germinal center B cell dynamics","volume":"45","author":"Mesin","year":"2016","journal-title":"Immunity"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0065-230X(02)86006-7","article-title":"The life and death of a B cell","volume":"86","author":"Defrance","year":"2002","journal-title":"Adv. Cancer Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.immuni.2008.07.016","article-title":"Fas receptor expression in germinal-center B cells is essential for T and B lymphocyte homeostasis","volume":"29","author":"Hao","year":"2008","journal-title":"Immunity"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1002\/jmv.21815","article-title":"FasL\/Fas pathway is involved in dengue virus induced apoptosis of the vascular endothelial cells","volume":"82","author":"Liao","year":"2010","journal-title":"J. Med. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4049\/jimmunol.1103350","article-title":"Association between magnitude of the virus-specific plasmablast response and disease severity in dengue patients","volume":"190","author":"Cordeiro","year":"2013","journal-title":"J. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Paranavitane, S.A., Gomes, L., Kamaladasa, A., Adikari, T.N., Wickramasinghe, N., Jeewandara, C., Shyamali, N.L., Ogg, G.S., and Malavige, G.N. (2014). Dengue NS1 antigen as a marker of severe clinical disease. BMC Infect. Dis., 14.","DOI":"10.1186\/s12879-014-0570-8"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1002\/jmv.23204","article-title":"Nonstructural protein NS1 immunodominant epitope detected specifically in dengue virus infected material by a SELDI-TOF\/MS based assay","volume":"84","author":"Steidel","year":"2012","journal-title":"J. Med. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"48","DOI":"10.4269\/ajtmh.2003.68.48","article-title":"Increased apoptosis and expression of tumor necrosis factor-alpha caused by infection of cultured human monocytes with dengue virus","volume":"68","author":"Espina","year":"2003","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Gandini, M., Gras, C., Azeredo, E.L., Pinto, L.M., Smith, N., Despres, P., da Cunha, R.V., de Souza, L.J., Kubelka, C.F., and Herbeuval, J.P. (2013). Dengue virus activates membrane TRAIL relocalization and IFN-a production by human plasmacytoid dendritic cells in vitro and in vivo. PLoS Neglected Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002257"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1002\/jmv.20004","article-title":"Apoptosis in dengue virus infected liver cell lines HepG2 and Hep3B","volume":"72","author":"Thongtan","year":"2004","journal-title":"J. Med. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"12312","DOI":"10.1128\/JVI.00968-08","article-title":"Enhancement by tumor necrosis factor alpha of dengue virus-induced endothelial cell production of reactive nitrogen and oxygen species is key to hemorrhage development","volume":"82","author":"Yen","year":"2008","journal-title":"J. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"657","DOI":"10.4049\/jimmunol.169.2.657","article-title":"Endothelial cell apoptosis induced by antibodies against dengue virus nonstructural protein 1 via production of nitric oxide","volume":"169","author":"Lin","year":"2002","journal-title":"J. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.4049\/jimmunol.1201976","article-title":"Anti-dengue virus nonstructural protein 1 antibodies cause NO-mediated endothelial cell apoptosis via ceramide-regulated glycogen synthase kinase-3beta and NF-kappaB activation","volume":"191","author":"Chen","year":"2013","journal-title":"J. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1002\/jmv.10261","article-title":"Antibodies from dengue patient sera cross-react with endothelial cells and induce damage","volume":"69","author":"Lin","year":"2003","journal-title":"J. Med. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Pattanapanyasat, K., Khowawisetsut, L., Chuansumrit, A., Chokephaibulkit, K., Tangnararatchakit, K., Apiwattanakul, N., Techasaensiri, C., Thitilertdecha, P., Sae-Ung, T., and Onlamoon, N. (2018). B cell subset alteration and the expression of tissue homing molecules in dengue infected patients. J. Biomed. Sci., 25.","DOI":"10.1186\/s12929-018-0467-8"},{"key":"ref_19","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_20","doi-asserted-by":"crossref","unstructured":"Balakrishnan, T., Bela-Ong, D.B., Toh, Y.X., Flamand, M., Devi, S., Koh, M.B., Hibberd, M.L., Ooi, E.E., Low, J.G., and Leo, Y.S. (2011). Dengue virus activates polyreactive, natural IgG B cells after primary and secondary infection. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0029430"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1128\/JVI.06075-11","article-title":"Rapid and massive virus-specific plasmablast responses during acute dengue virus infection in humans","volume":"86","author":"Wrammert","year":"2012","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zompi, S., Montoya, M., Pohl, M.O., Balmaseda, A., and Harris, E. (2012). Dominant cross-reactive B cell response during secondary acute dengue virus infection in humans. PLoS Neglected Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001568"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1023\/A:1025534223168","article-title":"Fas-induced apoptosis in B cells","volume":"8","author":"Mizuno","year":"2003","journal-title":"Apoptosis Int. J. Program. Cell Death"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5624","DOI":"10.4049\/jimmunol.152.12.5624","article-title":"Activation induces sensitivity toward APO-1 (CD95)-mediated apoptosis in human B cells","volume":"152","author":"Daniel","year":"1994","journal-title":"J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1182\/blood.V83.7.1856.1856","article-title":"Inverse expression of bcl-2 protein and Fas antigen in lymphoblasts in peripheral lymph nodes and activated peripheral blood T and B lymphocytes","volume":"83","author":"Yoshino","year":"1994","journal-title":"Blood"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4640","DOI":"10.4049\/jimmunol.1001946","article-title":"Anergic responses characterize a large fraction of human autoreactive naive B cells expressing low levels of surface IgM","volume":"186","author":"Quach","year":"2011","journal-title":"J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1002\/jmv.23832","article-title":"Apoptotic mediators in patients with severe and non-severe dengue from Brazil","volume":"86","author":"Limonta","year":"2014","journal-title":"J. Med. Virol."},{"key":"ref_28","first-page":"718","article-title":"B cells are the principal circulating mononuclear cells infected by dengue virus","volume":"30","author":"King","year":"1999","journal-title":"Southeast Asian J. Trop. Med. Public Health"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"12242","DOI":"10.1128\/JVI.76.23.12242-12249.2002","article-title":"Virus replication and cytokine production in dengue virus-infected human B lymphocytes","volume":"76","author":"Lin","year":"2002","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"13325","DOI":"10.1128\/JVI.01568-07","article-title":"Primary human splenic macrophages, but not T or B cells, are the principal target cells for dengue virus infection in vitro","volume":"81","author":"Blackley","year":"2007","journal-title":"J. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1002\/jmv.21051","article-title":"Monocytes, but not T or B cells, are the principal target cells for dengue virus (DV) infection among human peripheral blood mononuclear cells","volume":"80","author":"Kou","year":"2008","journal-title":"J. Med. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Correa, A.R., Berbel, A.C., Papa, M.P., Morais, A.T., Pecanha, L.M., and Arruda, L.B. (2015). Dengue virus directly stimulates polyclonal B cell activation. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0143391"},{"key":"ref_33","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_34","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1086\/340365","article-title":"Differing influences of virus burden and immune activation on disease severity in secondary dengue-3 virus infections","volume":"185","author":"Libraty","year":"2002","journal-title":"J. Infect. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1086\/315215","article-title":"Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severity","volume":"181","author":"Vaughn","year":"2000","journal-title":"J. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"901276","DOI":"10.1155\/2014\/901276","article-title":"Elevated dengue virus nonstructural protein 1 serum levels and altered toll-like receptor 4 expression, nitric oxide, and tumor necrosis factor alpha production in dengue hemorrhagic Fever patients","volume":"2014","author":"Carvalho","year":"2014","journal-title":"J. Trop. Med."},{"key":"ref_37","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_38","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_39","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_40","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1086\/506451","article-title":"Cellular immune activation in children with acute dengue virus infections is modulated by apoptosis","volume":"194","author":"Myint","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1038\/labinvest.2008.70","article-title":"Liver injury caused by antibodies against dengue virus nonstructural protein 1 in a murine model","volume":"88","author":"Lin","year":"2008","journal-title":"Lab. Investig. A J. Tech. Methods Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1111\/cei.12747","article-title":"Dengue NS1 antigen contributes to disease severity by inducing interleukin (IL)-10 by monocytes","volume":"184","author":"Adikari","year":"2016","journal-title":"Clin. Exp. Immunol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/4\/541\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:12:24Z","timestamp":1760029944000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/4\/541"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,8]]},"references-count":42,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["v17040541"],"URL":"https:\/\/doi.org\/10.3390\/v17040541","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,8]]}}}