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Evidence for the involvement of the RNA-dependent protein kinase (PKR) in the induction of human cytotoxic T lymphocytes against a synthetic peptide of HIV-1 by regulatory RNA

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Abstract

Exogenous RNA molecules can be incorporated into eukaryotic cells and can exert a variety of biological effects. We have previously showed that exogenous RNAs obtained from lymphoid organs of animals immunized with synthetic peptides of HIV-1 are able to induce cell-mediated immune responses. In this study, animals were immunized with a synthetic peptide (pol: 476–484) of HIV-1, referred to as p9, which is a cytotoxic T lymphocyte (CTL) epitope. The RNA extracted from the lymphoid organs of animals immunized with p9 was termed p9-RNA. We have demonstrated that p9-RNA is active in inducing human CTL. The p9-RNA was also able to activate the RNA-dependent protein kinase (PKR) of human lymphocytes. The polyA(+) p9-RNA was the fraction responsible for the activation of this protein kinase. We also found that p9-RNA activates the transcription factor nuclear kappa B (NF-κB) by inducing the degradation of its inhibitor I-κB. Thus, these findings suggest that p9-RNA may act as a regulatory RNA and that the induction of CTL activity by p9-RNA could be mediated by PKR through NF-κB activation. It is known that CTL activity plays an important role in host defense against HIV-1 infection. Elucidating the molecular mechanism of p9-RNA could contribute to determining the basis for the use of p9-RNA as an immunomodulator in HIV-infected patients.

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Authors and Affiliations

  1. Department of Biochemistry and Immunology, School of Medicine University of São Paulo, Ribeirão Preto, S.P., Brazil

    Fernando L. De Lucca, Valeria S.F. Sales, Liliana R. Souza & Maria Angelica E. Watanabe

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  1. Fernando L. De Lucca
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  2. Valeria S.F. Sales
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  3. Liliana R. Souza
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  4. Maria Angelica E. Watanabe
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De Lucca, F.L., Sales, V.S., Souza, L.R. et al. Evidence for the involvement of the RNA-dependent protein kinase (PKR) in the induction of human cytotoxic T lymphocytes against a synthetic peptide of HIV-1 by regulatory RNA. Mol Cell Biochem 238, 19–26 (2002). https://doi.org/10.1023/A:1019983102017

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