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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

Kumar, Priti and Krishna, Venkatramana D and Sulochana, Paramadevanapalli and Nirmala, Gejjehalli and Haridattatreya, Maganti and Satchidanandam, Vijaya (2004) 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. In: Journal of General Virology, 85 (2). pp. 471-482.

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Abstract

Japanese encephalitis virus (JEV), a single-stranded positive-sense RNA virus of the family Flaviviridae, 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 Human immunodeficiency virus to transduce proteins across cell membranes, facilitating intracellular protein delivery followin exogenous addition to cultured cells, prompted us to express the four largest proteins of JEV, comprising 71% of the JEV genome coding sequence, as Tat fusions for enumerating the frequencies of virus-specific $CD4^+$ and $CD8^+$ 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% 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.

Item Type: Journal Article
Additional Information: The copyright belongs to Society for General Microbiology.
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited: 27 May 2006
Last Modified: 19 Sep 2010 04:27
URI: http://eprints.iisc.ernet.in/id/eprint/6828

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