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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-kappaB) by inducing the degradation of its inhibitor I-kappaB. 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-kappaB 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.

Activation of the RNA-Dependent Protein Kinase (PKR) of Lymphocytes by Regulatory RNAs: Implications for Immunomodulation in HIV Infection

“…The p9 is an HLA-A2-restricted peptide, which binds with a high affinity to A2 molecules on intact cells [4] and taking advantage of this property, this CTL epitope was used in the cytotoxicity assays. Thus, it has been shown that RNA isolated from lymphocytes of animals immunized with the synthetic peptide p9, named p9-RNA, is active in inducing in vitro human CTLs against naïve lymphocytes previously incubated with p9 [29]. This result is relevant, since this cellular immune response was directed against an immunodominant and highly conserved CTL epitope.…”