RNA-mediated activation of the transcription factor NF-kappa B in human lymphocytes: Implications for HIV immunopathogenesis?

Apoptosis of lymphocytes in HIV infection is triggered through upregulation of Fas and Fas receptor expression. Recent studies indicated a direct link between NF-KB activation and the expression of Fas. It is known that NF-KB is activated by degradation of its inhibitor I-KB alpha. We found that p9- RNA, isolated from animals immunized with the synthetic peptide p9 of HIV-I , activates the RNA-dependent protein kinase (PKR) which phosphorylates I-K Ba. Since the phosphorylation of I-KBa is accompanied by its degradation, w e have investigated the ability of p9-RNA to induce degradation of I-kB alp ha. Fire detected the degradation of I-KB alpha in p9-RNA-treated human lym phocytes indicating that p9-RNA induces NF-KB activation and is acting as a regulatory RNA. These findings suggest that regulatory RNAs could be invol ved in the immunopathogenesis of HIV infection.