Anti-human immunodeficiency virus-1 (HIV-1) polyamide (peptide) nucleic acids (PNAs) conjugated with cell-penetrating peptides (CPPs) targeted to the viral genome are potent virucidal and antiviral agents. Earlier, we have shown that the anti-HIV-1 PNATAR-penetratin conjugate is rapidly taken up by cells and is nontoxic to mice when administered at repeat doses of as high as 100 mg/kg body weight. In the present studies we demonstrate that naked PNATAR is immunologically inert as judged by the proliferation responses of splenocytes and lymph node cells from PNATAR-immunized mice challenged with the immunizing antigen. In contrast, PNA TAR-penetratin conjugate is moderately immunogenic mainly due to its penetratin peptide component. Cytokine secretion profiles of the lymph node cells from the conjugate-immunized mice showed marginally elevated levels of proinflammatory cytokines, which are known to promote proliferation of T lymphocytes. Since the candidate compound, PNATAR-penetratin conjugate displays potent virucidal and antiviral activities against HIV-1, the favorable immunological response together with negligible toxicity suggest a strong therapeutic potential for this class of compounds.
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Molecular Biology