Peptide Nucleic Acids Stimulate Gamma Interferon and Inhibit the Replication of the Human Immunodeficiency Virus

Abstract

Background

Peptide nucleic acids (PNAs) are newly appreciated molecules consisting of both amino acids and nucleotides that already have been shown to have interesting properties; for example, they are very stable and have anti-sense activity. Reticulose, a peptide nucleic acid preparation that had been used for many years to treat human viral infections such as influenza, was investigated for inhibitory effects on the replication of the human immunodeficiency virus (HIV) in cell culture systems.

Methods

H9 and peripheral blood mononuclear cells (PBMCs) were treated with reticulose before, during, and after infection with HIV-1 at various multiplicities. Treatment of cells with PNA significantly inhibited replication of HIV-1 as measured by synthesis of viral mRNA and p24 protein, reverse transcriptase activity, and syncitial cell formation. Exposure of cells to PNA under conditions that favor transfection of DNA, such as electroporation, markedly enhanced the inhibition of HIV replication.

Results

In experiments to examine the mechanism of inhibition, it was found that PNA stimulated production of a distinctive cassette of chemokine mRNAs in PBMC cultures. Cytokines stimulated by reticulose included gamma interferon, interleukin-6, interleukin-1, and tissue necrosis factor-alpha.

Conclusions

These results offer new tools for the study of immune functions and, moreover, open new approaches to the therapy of HIV infection and AIDS.