{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T09:06:47Z","timestamp":1758704807972},"reference-count":39,"publisher":"Microbiology Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,2,1]]},"abstract":"<jats:p><jats:italic>Japanese encephalitis virus<\/jats:italic>(JEV), a single-stranded positive-sense RNA virus of the family<jats:italic>Flaviviridae<\/jats:italic>, is the major cause of paediatric encephalitis in Asia. The high incidence of subclinical infections in Japanese encephalitis-endemic areas and subsequent evasion of encephalitis points to the development of immune responses against JEV. Humoral responses play a central role in protection against JEV; however, cell-mediated immune responses contributing to this end are not fully understood. The structural envelope (E) protein, the major inducer of neutralizing antibodies, is a poor target for T cells in natural JEV infections. The extent to which JEV non-structural proteins are targeted by T cells in subclinically infected healthy children would help to elucidate the role of cell-mediated immunity in protection against JEV as well as other flaviviral infections. The property of the Tat peptide of<jats:italic>Human immunodeficiency virus<\/jats:italic>to transduce proteins across cell membranes, facilitating intracellular protein delivery following exogenous addition to cultured cells, prompted us to express the four largest proteins of JEV, comprising 71\u200a% of the JEV genome coding sequence, as Tat fusions for enumerating the frequencies of virus-specific CD4<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>T cells in JEV-immune donors. At least two epitopes recognized by distinct HLA alleles were found on each of the non-structural proteins, with dominant antiviral Th1 T cell responses to the NS3 protein in nearly 96\u200a% of the cohort. The data presented here show that non-structural proteins are frequently targeted by T cells in natural JEV infections and may be efficacious supplements for the predominantly antibody-eliciting E-based JEV vaccines.<\/jats:p>","DOI":"10.1099\/vir.0.19531-0","type":"journal-article","created":{"date-parts":[[2004,2,9]],"date-time":"2004-02-09T22:07:58Z","timestamp":1076364478000},"page":"471-482","source":"Crossref","is-referenced-by-count":23,"title":["Cell-mediated immune responses in healthy children with a history of subclinical infection with Japanese encephalitis virus: analysis of CD4+ and CD8+ T cell target specificities by intracellular delivery of viral proteins using the human immunodeficiency virus Tat protein transduction domain"],"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, 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