{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T05:27:31Z","timestamp":1761974851995},"reference-count":41,"publisher":"Microbiology Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,5,1]]},"abstract":"<jats:p>Our earlier identification of the non-structural protein 3 (NS3) of Japanese encephalitis virus (JEV) as a dominant CD4<jats:sup>+<\/jats:sup>as well as CD8<jats:sup>+<\/jats:sup>T cell-eliciting antigen in a healthy JEV-endemic cohort with a wide HLA distribution implied the presence of several epitopes dispersed over the length of the protein. Use of various truncated versions of NS3 in lymphocyte stimulation and interferon (IFN)-<jats:italic>\u03b3<\/jats:italic>secretion assays revealed that amino acids (aa) 193\u2013324 of NS3 were comparable with, if not superior to, the full-length protein in evoking Th1 responses. The potential of this 14\u00b74\u2005kDa stretch to stimulate IFN-<jats:italic>\u03b3<\/jats:italic>production from both subtypes of T cells in a manner qualitatively and quantitatively similar to the 68\u2005kDa parent protein suggested the presence within it of both class I and II epitopes and demonstrated that the entire immunogenicity of NS3 was focused on aa 193\u2013324. Interestingly, this segment contained five of the eight helicase motifs of NS3. Analysis of variability of the NS3 protein sequence across 16 JEV isolates revealed complete identity of aa 219\u2013318, which is contained within the above segment, suggesting that NS3-specific epitopes tend to cluster in relatively conserved regions that harbour functionally critical domains of the protein.<\/jats:p>","DOI":"10.1099\/vir.0.19698-0","type":"journal-article","created":{"date-parts":[[2004,4,22]],"date-time":"2004-04-22T21:53:02Z","timestamp":1082670782000},"page":"1131-1143","source":"Crossref","is-referenced-by-count":24,"title":["Conserved amino acids 193\u2013324 of non-structural protein 3 are a dominant source of peptide determinants for CD4+ and CD8+ T cells in a healthy Japanese encephalitis virus-endemic cohort"],"prefix":"10.1099","volume":"85","author":[{"given":"Priti","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, Karnataka 560012, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paramadevanapalli","family":"Sulochana","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Vijayanagar Institute of Medical Sciences, Bellary, Karnataka 583104, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gejjehalli","family":"Nirmala","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Vijayanagar Institute of Medical Sciences, Bellary, Karnataka 583104, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maganti","family":"Haridattatreya","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Vijayanagar Institute of Medical Sciences, Bellary, Karnataka 583104, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vijaya","family":"Satchidanandam","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, Karnataka 560012, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"crossref","first-page":"8032","DOI":"10.1128\/JVI.72.10.8032-8036.1998","article-title":"Establishment and characterization of Japanese encephalitis virus-specific, human CD4+ T-cell clones: flavivirus cross-reactivity, protein recognition, and cytotoxic activity","volume":"72","author":"Aihara","year":"1998","journal-title":"J Virol"},{"key":"R2","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1006\/meth.2001.1186","article-title":"TAT-mediated protein transduction into mammalian cells","volume":"24","author":"Becker-Hapak","year":"2001","journal-title":"Methods"},{"key":"R3","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1099\/0022-1317-81-3-781","article-title":"Phylogeny of the genus Flavivirus using complete coding sequences of arthropod-borne viruses and viruses with no known vector","volume":"81","author":"Billoir","year":"2000","journal-title":"J Gen Virol"},{"key":"R4","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1006\/viro.2001.1255","article-title":"Human cytotoxic T lymphocyte responses to live attenuated 17D yellow fever vaccine: identification of HLA-B35-restricted CTL epitopes on nonstructural proteins NS1, NS2b, NS3, and the structural protein E","volume":"293","author":"Co","year":"2002","journal-title":"Virology"},{"key":"R5","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1111\/j.1348-0421.1995.tb02200.x","article-title":"Proliferative response of human peripheral blood mononuclear cells to Japanese encephalitis virus","volume":"39","author":"Desai","year":"1995","journal-title":"Microbiol Immunol"},{"key":"R6","doi-asserted-by":"crossref","first-page":"6011","DOI":"10.1128\/JVI.71.8.6011-6019.1997","article-title":"Immunodominant CD4+ T-cell epitope within nonstructural protein 3 in acute hepatitis C virus infection","volume":"71","author":"Diepolder","year":"1997","journal-title":"J Virol"},{"key":"R7","first-page":"95","article-title":"Bioedit: a user-friendly biological sequence alignment editor and analysis program for Windows 95\/98\/NT","volume":"41","author":"Hall","year":"1999","journal-title":"Nucleic Acids Symp Ser"},{"key":"R8","doi-asserted-by":"crossref","first-page":"278","DOI":"10.4269\/ajtmh.1995.53.278","article-title":"Japanese encephalitis virus-specific proliferative responses of human peripheral blood T lymphocytes","volume":"53","author":"Konishi","year":"1995","journal-title":"Am J Trop Med Hyg"},{"key":"R9","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1002\/jmv.1890440204","article-title":"Homologous and heterologous neutralization antibody responses after immunization with Japanese encephalitis vaccine among Taiwan children","volume":"44","author":"Ku","year":"1994","journal-title":"J Med Virol"},{"key":"R10","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1128\/IAI.71.4.1929-1937.2003","article-title":"The Apa protein of Mycobacterium tuberculosis stimulates gamma interferon-secreting CD4+ and CD8+ T cells from purified protein derivative-positive individuals and affords protection in a guinea pig model","volume":"71","author":"Kumar","year":"2003a","journal-title":"Infect Immun"},{"key":"R11","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1007\/s00705-003-0118-5","article-title":"Screening for T cell-eliciting proteins of Japanese encephalitis virus in a healthy JE-endemic human cohort using recombinant baculovirus-infected insect cell preparations","volume":"148","author":"Kumar","year":"2003b","journal-title":"Arch Virol"},{"key":"R12","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1099\/vir.0.19531-0","article-title":"Cell mediated immune responses in healthy children with a history of Japanese encephalitis virus subclinical infection: analysis of CD4+ and CD8+ T cell target specificities by intracellular delivery of viral proteins using the HIV Tat protein transduction domain","volume":"85","author":"Kumar","year":"2004a","journal-title":"J Gen Virol"},{"key":"R13","doi-asserted-by":"crossref","DOI":"10.1086\/381768","article-title":"Impaired Th1 function of NS3-specific T cells in Japanese encephalitis patients with neurological sequelae","author":"Kumar","year":"2004b","journal-title":"J Infect Dis"},{"key":"R14","doi-asserted-by":"crossref","first-page":"6285","DOI":"10.1128\/JVI.67.10.6285-6288.1993","article-title":"Definition of an HLA-DPw2-restricted epitope on NS3, recognized by a dengue virus serotype-cross-reactive human CD4+ CD8\u2212 cytotoxic T-cell clone","volume":"67","author":"Kurane","year":"1993","journal-title":"J Virol"},{"key":"R15","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.1099\/0022-1317-76-9-2243","article-title":"Flavivirus-cross-reactive, HLA-DR15-restricted epitope on NS3 recognized by human CD4+ CD8\u2212 cytotoxic T lymphocyte clones","volume":"76","author":"Kurane","year":"1995","journal-title":"J Gen Virol"},{"key":"R16","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1006\/viro.1997.8925","article-title":"Definition of an epitope on NS3 recognized by human CD4+ cytotoxic T lymphocyte clones cross-reactive for dengue virus types 2, 3, and 4","volume":"240","author":"Kurane","year":"1998","journal-title":"Virology"},{"key":"R17","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1002\/hep.510300435","article-title":"Conserved hepatitis C virus sequences are highly immunogenic for CD4+ T cells: implications for vaccine development","volume":"30","author":"Lamonaca","year":"1999","journal-title":"Hepatology"},{"key":"R18","first-page":"313","article-title":"Rates and dates of divergence between AIDS virus nucleotide sequences","volume":"5","author":"Li","year":"1988","journal-title":"Mol Biol Evol"},{"key":"R19","doi-asserted-by":"crossref","first-page":"8798","DOI":"10.1128\/JVI.73.10.8798-8807.1999","article-title":"Structure-based mutagenesis study of hepatitis C virus NS3 helicase","volume":"73","author":"Lin","year":"1999","journal-title":"J Virol"},{"key":"R20","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1006\/viro.1994.1335","article-title":"The flavivirus nonstructural protein NS3 is a dominant source of cytotoxic T cell peptide determinants","volume":"202","author":"Lobigs","year":"1994","journal-title":"Virology"},{"key":"R21","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1086\/324320","article-title":"Strong HLA class I-restricted T cell responses in dengue hemorrhagic fever: a double-edged sword?","volume":"184","author":"Loke","year":"2001","journal-title":"J Infect Dis"},{"key":"R22","doi-asserted-by":"crossref","first-page":"497","DOI":"10.3201\/eid0707.017703","article-title":"Emerging viral diseases of southeast Asia and the western Pacific","volume":"7","author":"Mackenzie","year":"2001","journal-title":"Emerg Infect Dis"},{"key":"R23","article-title":"Japanese Encephalitis and West Nile Viruses .","volume-title":"Current Topics in Microbiology and Immunology","volume":"vol.\u2005267","author":"Mackenzie","year":"2002"},{"key":"R24","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1172\/JCI118964","article-title":"Dominant recognition by human CD8+ cytotoxic T lymphocytes of dengue virus nonstructural proteins NS3 and NS1.2a","volume":"98","author":"Mathew","year":"1996","journal-title":"J Clin Invest"},{"key":"R25","doi-asserted-by":"crossref","first-page":"3999","DOI":"10.1128\/JVI.72.5.3999-4004.1998","article-title":"Predominance of HLA-restricted cytotoxic T-lymphocyte responses to serotype-cross-reactive epitopes on nonstructural proteins following natural secondary dengue virus infection","volume":"72","author":"Mathew","year":"1998","journal-title":"J Virol"},{"key":"R26","doi-asserted-by":"crossref","first-page":"9633","DOI":"10.1128\/JVI.75.20.9633-9643.2001","article-title":"Mutagenesis of the dengue virus type 2 NS3 protein within and outside helicase motifs: effects on enzyme activity and virus replication","volume":"75","author":"Matusan","year":"2001","journal-title":"J Virol"},{"key":"R27","first-page":"815","article-title":"Yellow fever","volume-title":"In Vaccines","author":"Monath","year":"1999"},{"key":"R28","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1099\/0022-1317-79-4-697","article-title":"Definition of the region on NS3 which contains multiple epitopes recognized by dengue virus serotype-cross-reactive and flavivirus-cross-reactive, HLA-DPw2-restricted CD4+ T cell clones","volume":"79","author":"Okamoto","year":"1998","journal-title":"J Gen Virol"},{"key":"R29","doi-asserted-by":"crossref","first-page":"11457","DOI":"10.1128\/JVI.75.23.11457-11463.2001","article-title":"Protective mechanisms induced by a Japanese encephalitis virus DNA vaccine: requirement for antibody but not CD8+ cytotoxic T-cell responses","volume":"75","author":"Pan","year":"2001","journal-title":"J Virol"},{"key":"R30","first-page":"301","article-title":"Safety and efficacy of Japanese encephalitis vaccine produced in India","volume":"88","author":"Rao-Bhau","year":"1988","journal-title":"Indian J Med Res"},{"key":"R31","doi-asserted-by":"crossref","first-page":"3820","DOI":"10.4049\/jimmunol.166.6.3820","article-title":"Antiviral cytotoxic T cells cross-reactively recognize disparate peptide determinants from related viruses but ignore more similar self- and foreign determinants","volume":"166","author":"Regner","year":"2001","journal-title":"J Immunol"},{"key":"R32","first-page":"991","article-title":"Flaviviridae","volume-title":"In Fields Virology","author":"Rice","year":"2001"},{"key":"R33","doi-asserted-by":"crossref","first-page":"3984","DOI":"10.1128\/JVI.75.8.3984-3987.2001","article-title":"Degenerate immunogenicity of an HLA-A2-restricted hepatitis B virus nucleocapsid cytotoxic T-lymphocyte epitope that is also presented by HLA-B51","volume":"75","author":"Thimme","year":"2001","journal-title":"J Virol"},{"key":"R34","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0166-0934(00)00293-7","article-title":"Development of a simplified assay for the detection of neutralizing antibodies to Japanese encephalitis virus","volume":"93","author":"Ting","year":"2001","journal-title":"J Virol Methods"},{"key":"R35","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1002\/1521-4141(200009)30:9<2521::AID-IMMU2521>3.0.CO;2-Q","article-title":"A single CTL clone can recognize a naturally processed HIV-1 epitope presented by two different HLA class I molecules","volume":"30","author":"Tomiyama","year":"2000","journal-title":"Eur J Immunol"},{"key":"R36","first-page":"672","article-title":"Japanese encephalitis vaccines","volume-title":"In Vaccines","author":"Tsai","year":"1999"},{"key":"R37","doi-asserted-by":"crossref","first-page":"8757","DOI":"10.1128\/JVI.76.17.8757-8768.2002","article-title":"Clustering patterns of cytotoxic T-lymphocyte epitopes in human immunodeficiency virus type 1 (HIV-1) proteins reveal imprints of immune evasion on HIV-1 global variation","volume":"76","author":"Yusim","year":"2002","journal-title":"J Virol"},{"key":"R38","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1073\/pnas.93.2.548","article-title":"Population dynamics of flaviviruses revealed by molecular phylogenies","volume":"93","author":"Zanotto","year":"1996","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R39","doi-asserted-by":"crossref","first-page":"3108","DOI":"10.1128\/JVI.70.5.3108-3117.1996","article-title":"Identification of amino acids involved in recognition by dengue virus NS3-specific, HLA-DR15-restricted cytotoxic CD4+ T-cell clones","volume":"70","author":"Zeng","year":"1996","journal-title":"J Virol"},{"key":"R40","doi-asserted-by":"crossref","first-page":"5959","DOI":"10.4049\/jimmunol.168.11.5959","article-title":"T cell responses to an HLA-B*07-restricted epitope on the dengue NS3 protein correlate with disease severity","volume":"168","author":"Zivna","year":"2002","journal-title":"J Immunol"},{"key":"R41","doi-asserted-by":"crossref","first-page":"2754","DOI":"10.4049\/jimmunol.163.5.2754","article-title":"Partial agonist effect influences the CTL response to a heterologous dengue virus serotype","volume":"163","author":"Zivny","year":"1999","journal-title":"J Immunol"}],"container-title":["Journal of General Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jgv\/10.1099\/vir.0.19698-0?crawler=true","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T12:31:41Z","timestamp":1682685101000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jgv\/10.1099\/vir.0.19698-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,5,1]]},"references-count":41,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2004,5,1]]}},"URL":"https:\/\/doi.org\/10.1099\/vir.0.19698-0","relation":{},"ISSN":["0022-1317","1465-2099"],"issn-type":[{"value":"0022-1317","type":"print"},{"value":"1465-2099","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,5,1]]}}}