{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T17:47:36Z","timestamp":1761155256010},"reference-count":39,"publisher":"Microbiology Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,4,1]]},"abstract":"<jats:p>Japanese encephalitis is an acute infection of the central nervous system caused by Japanese encephalitis virus (JEV). The importance of an effective humoral response in preventing JEV infection has already been established, although the contribution of cellular immunity remains unclear. This study used an experimental murine model to understand the protective effects of cell-mediated immunity in JEV infection. Fourteen-day-old mice adoptively transferred with JEV-immune splenocytes were found to be protected from peripheral JEV challenge. The survival rate was reduced when transferred cells were depleted of their CD4<jats:sup>+<\/jats:sup> T-cell population. Correspondingly, increased protection was observed when JEV-primed isolated CD4<jats:sup>+<\/jats:sup> T cells were transferred compared with isolated CD8<jats:sup>+<\/jats:sup> T cells. Mice protected from JEV infection by the adoptive transfer of JEV-immune splenocytes had higher levels of immunomodulatory cytokines and decreased expression of pro-inflammatory cytokines. Concurrent with the increase in Th2 cytokines, JEV-specific IgM and IgG1 antibody titres were found to be elevated in protected mice. Taken together, these data indicate a definite role for CD4<jats:sup>+<\/jats:sup> T cells in protection from lethal JEV infection in na\u00efve 14-day-old mice. Induction of a Th2 cytokine response and IgG1 antibody probably achieves an immunomodulatory effect that results in the enhanced survival of these animals.<\/jats:p>","DOI":"10.1099\/vir.0.008045-0","type":"journal-article","created":{"date-parts":[[2009,3,10]],"date-time":"2009-03-10T18:38:47Z","timestamp":1236710327000},"page":"818-826","source":"Crossref","is-referenced-by-count":26,"title":["Japanese encephalitis virus produces a CD4+ Th2 response and associated immunoprotection in an adoptive-transfer murine model"],"prefix":"10.1099","volume":"90","author":[{"given":"S. M.","family":"Biswas","sequence":"first","affiliation":[{"name":"National Institute of Virology, Sus Road Campus, Pashan, Pune 411021, Maharashtra, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V. M.","family":"Ayachit","sequence":"additional","affiliation":[{"name":"National Institute of Virology, Sus Road Campus, Pashan, Pune 411021, Maharashtra, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. N.","family":"Sapkal","sequence":"additional","affiliation":[{"name":"National Institute of Virology, Sus Road Campus, Pashan, Pune 411021, Maharashtra, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. A.","family":"Mahamuni","sequence":"additional","affiliation":[{"name":"National Institute of Virology, Sus Road Campus, Pashan, Pune 411021, Maharashtra, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. M.","family":"Gore","sequence":"additional","affiliation":[{"name":"National Institute of Virology, Sus Road Campus, Pashan, Pune 411021, Maharashtra, 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":"190","DOI":"10.1179\/016164106X98062","article-title":"Inflammatory markers in the patients of Japanese encephalitis","volume":"28","author":"Babu","year":"2006","journal-title":"Neurol Res"},{"key":"R3","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1086\/376870","article-title":"Prophylactic and therapeutic efficacy of human intravenous immunoglobulin in treating West Nile infection in mice","volume":"188","author":"Ben-Nathan","year":"2003","journal-title":"J Infect Dis"},{"key":"R4","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1093\/infdis\/151.6.1093","article-title":"Kinetics of IgM and IgG responses to Japanese encephalitis virus in human serum and cerebrospinal fluid","volume":"151","author":"Burke","year":"1985","journal-title":"J Infect Dis"},{"key":"R5","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1128\/JVI.77.4.2578-2586.2003","article-title":"B cells and antibody play critical roles in the immediate defense of disseminated infection by West Nile encephalitis virus","volume":"77","author":"Diamond","year":"2003","journal-title":"J Virol"},{"key":"R6","first-page":"368","article-title":"Epitope analysis of strains of Japanese encephalitis virus by monoclonal antibodies","volume":"89","author":"Ghosh","year":"1989","journal-title":"Indian J Med Res"},{"key":"R7","doi-asserted-by":"crossref","first-page":"118","DOI":"10.3181\/00379727-123-31418","article-title":"The effect of host age, virus dose and route of inoculation on inapparent infection in mice with Japanese encephalitis virus","volume":"123","author":"Grossberg","year":"1966","journal-title":"Proc Soc Exp Biol Med"},{"key":"R8","doi-asserted-by":"crossref","first-page":"9208","DOI":"10.1128\/JVI.72.11.9208-9216.1998","article-title":"Evidence for an underlying CD4 helper and CD8 T-cell defect in B-cell-deficient mice: failure to clear persistent virus infection after adoptive immunotherapy with virus-specific memory cells from\u200a\u03bcMT\/\u03bcMT mice","volume":"72","author":"Homann","year":"1998","journal-title":"J Virol"},{"key":"R9","first-page":"153","article-title":"Japanese encephalitis virus is an important cause of encephalitis among children in Cuddalore district","volume":"31","author":"Kabilan","year":"2004","journal-title":"Tamil Nadu, India. J Clin Virol"},{"key":"R10","first-page":"1040","article-title":"CD4+ T lymphocytes play a crucial role in antibody production and tumor immunity against simian virus 40 large tumor antigen","volume":"63","author":"Kennedy","year":"2003","journal-title":"Cancer Res"},{"key":"R11","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0065-3527(03)60004-7","article-title":"Immune modulation by flaviviruses","volume":"60","author":"King","year":"2003","journal-title":"Adv Virus Res"},{"key":"R12","doi-asserted-by":"crossref","first-page":"525","DOI":"10.3201\/eid1203.051251","article-title":"Japanese encephalitis, Singapore","volume":"12","author":"Koh","year":"2006","journal-title":"Emerg Infect Dis"},{"key":"R13","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":"R14","doi-asserted-by":"crossref","first-page":"3675","DOI":"10.1016\/S0264-410X(03)00382-7","article-title":"Comparison of protective efficacies of plasmid DNAs encoding Japanese encephalitis virus proteins that induce neutralizing antibody or cytotoxic T lymphocytes in mice","volume":"21","author":"Konishi","year":"2003","journal-title":"Vaccine"},{"key":"R15","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1007\/s00705-003-0118-5","article-title":"Screening for T cell-eliciting protein of Japanese encephalitis virus in a healthy JE-endemic human cohort using recombinant baculovirus-infected insect cell preparations","volume":"148","author":"Kumar","year":"2003","journal-title":"Arch Virol"},{"key":"R16","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1086\/381768","article-title":"Impaired T helper 1 function of non-structural protein 3-specific T cells in Japanese encephalitis patients with neurological sequelae","volume":"189","author":"Kumar","year":"2004","journal-title":"J Infect Dis"},{"key":"R17","doi-asserted-by":"crossref","first-page":"3202","DOI":"10.1128\/JVI.76.7.3202-3211.2002","article-title":"Lack of both Fas ligand and perforin protects from flavivirus-mediated encephalitis in mice","volume":"76","author":"Licon Luna","year":"2002","journal-title":"J Virol"},{"key":"R18","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1128\/JVI.75.5.2107-2118.2001","article-title":"Yellow fever virus encephalitis: properties of the brain-associated T-cell response during virus clearance in normal and gamma interferon-deficient mice and requirement for CD4+ lymphocytes","volume":"75","author":"Liu","year":"2001","journal-title":"J Virol"},{"key":"R19","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1016\/S0140-6736(05)67543-5","article-title":"Japanese encephalitis: the need for a more effective vaccine","volume":"366","author":"Marfin","year":"2005","journal-title":"Lancet"},{"key":"R20","doi-asserted-by":"crossref","first-page":"5141","DOI":"10.1128\/JVI.65.10.5141-5148.1991","article-title":"T-helper cell and associated antibody response to synthetic peptides of the E glycoprotein of Murray Valley encephalitis virus","volume":"65","author":"Mathews","year":"1991","journal-title":"J Virol"},{"key":"R21","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1099\/0022-1317-64-4-805","article-title":"Host defence mechanisms against Japanese encephalitis virus infection in mice","volume":"64","author":"Mathur","year":"1983","journal-title":"J Gen Virol"},{"key":"R22","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1099\/0022-1317-77-4-705","article-title":"Protection of adult but not newborn mice against lethal intracerebral challenge with Japanese encephalitis virus by adoptively transferred virus-specific cytotoxic T lymphocytes: requirement for L3T4+ T cells","volume":"77","author":"Murali-Krishna","year":"1996","journal-title":"J Gen Virol"},{"key":"R23","doi-asserted-by":"crossref","first-page":"6325","DOI":"10.1128\/JVI.64.12.6325-6328.1990","article-title":"Rotavirus-specific cytotoxic T lymphocytes passively protect against gastroenteritis in suckling mice","volume":"64","author":"Offit","year":"1990","journal-title":"J Virol"},{"key":"R24","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":"R25","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.3201\/eid1209.060200","article-title":"Japanese encephalitis outbreak, India, 2005","volume":"12","author":"Parida","year":"2006","journal-title":"Emerg Infect Dis"},{"key":"R26","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1099\/0022-1317-72-7-1645","article-title":"Preliminary analysis of murine cytotoxic T cell responses to the proteins of the flavivirus Kunjin using vaccinia virus expression","volume":"72","author":"Parrish","year":"1991","journal-title":"J Gen Virol"},{"key":"R27","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1002\/(SICI)1096-9071(199702)51:2<132::AID-JMV8>3.0.CO;2-8","article-title":"Correlation of tumor necrosis factor levels in the serum and cerebrospinal fluid with clinical outcome in Japanese encephalitis patients","volume":"51","author":"Ravi","year":"1997","journal-title":"J Med Virol"},{"key":"R28","first-page":"493","article-title":"A simple method of estimating fifty percent end points","volume":"27","author":"Reed","year":"1938","journal-title":"Am J Hyg"},{"key":"R29","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1111\/j.1749-6632.2001.tb02704.x","article-title":"Antibody prophylaxis and therapy for flaviviral encephalitis infections","volume":"951","author":"Roehrig","year":"2001","journal-title":"Ann N Y Acad Sci"},{"key":"R30","doi-asserted-by":"crossref","first-page":"8312","DOI":"10.1128\/JVI.78.15.8312-8321.2004","article-title":"Role of CD8+ T cells in control of West Nile infection","volume":"78","author":"Shrestha","year":"2004","journal-title":"J Virol"},{"key":"R31","doi-asserted-by":"crossref","first-page":"12060","DOI":"10.1128\/JVI.01650-06","article-title":"CD4+ T-cell responses are required for clearance of West Nile virus from the central nervous system","volume":"80","author":"Sitati","year":"2006","journal-title":"J Virol"},{"key":"R32","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1002\/micr.1055","article-title":"Development of the blood\u2013nerve barrier in neonatal rats","volume":"21","author":"Smith","year":"2001","journal-title":"Microsurgery"},{"key":"R33","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.virol.2005.05.011","article-title":"CD4 T cell control of acute and latent murine gammaherpesvirus infection requires IFN \u03b3","volume":"338","author":"Sparks-Thissen","year":"2005","journal-title":"Virology"},{"key":"R34","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.1128\/JVI.01762-07","article-title":"CD4 T cells contribute to virus control and pathology following CNS infection by neurotropic mouse hepatitis virus","volume":"82","author":"Stohlman","year":"2008","journal-title":"J Virol"},{"key":"R35","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0165-5728(01)00444-1","article-title":"IL-10 promotes survival of microglia without activating Akt","volume":"122","author":"Strle","year":"2002","journal-title":"J Neuroimmunol"},{"key":"R36","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1007\/s007050050043","article-title":"Definition of an epitope on Japanese encephalitis virus (JEV) envelope protein recognized by JEV-specific murine CD8+ cytotoxic T lymphocytes","volume":"145","author":"Takada","year":"2000","journal-title":"Arch Virol"},{"key":"R37","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.virol.2006.01.050","article-title":"CD4 T cell control primary measles virus infection of the CNS: regulation is dependent on combined activity with either CD8 T cells or with B cells: CD4, CD8 or B cells alone are ineffective","volume":"347","author":"Tishon","year":"2006","journal-title":"Virology"},{"key":"R38","doi-asserted-by":"crossref","first-page":"13323","DOI":"10.1128\/JVI.77.24.13323-13334.2003","article-title":"CD8+ T cells mediate recovery and immunopathology in West Nile virus encephalitis","volume":"77","author":"Wang","year":"2003","journal-title":"J Virol"},{"key":"R39","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1086\/423328","article-title":"Proinflammatory cytokines and chemokines in humans with Japanese encephalitis","volume":"190","year":"2004","journal-title":"J Infect Dis"}],"container-title":["Journal of General Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jgv\/10.1099\/vir.0.008045-0?crawler=true","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T14:29:44Z","timestamp":1603808984000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jgv\/10.1099\/vir.0.008045-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,4,1]]},"references-count":39,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2009,4,1]]}},"URL":"https:\/\/doi.org\/10.1099\/vir.0.008045-0","relation":{},"ISSN":["0022-1317","1465-2099"],"issn-type":[{"value":"0022-1317","type":"print"},{"value":"1465-2099","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,4,1]]}}}