Blocking of Human Immunodeficiency Virus Type-1 Virion Autolysis by Autologous p2^gag Peptide

Abstract

Our previous study suggested that the p2^gag peptide, AEAMSQVTNTATIM, inhibits human immunodeficiency virus type 1 (HIV-1) protease (PR) activity in vitro. In this study, Ala substitutions (Met4Ala and Thr8Ala) and deletion of amino acid Asn9 within the nona p2^gag peptide (AEAMSQVTN) were found to decrease the inhibitory effect on HIV-1 PR activity. Furthermore, treatment of PMA-activated latently infected T lymphocytes, ACH-2 cells, with the p2^gag peptide (100 and 250 μM) resulted in a decrease in the amount of p24^gag in the resultant viral lysates derived from the cell-free supernatant. In addition, the HIV-1-Tat-p2^gag fusion peptide was synthesized to effectively deliver the p2^gag peptide into the cells. The fusion peptide was incorporated into chronically infected T lymphocytes, CEM/LAV1 cells, as detected on indirect immunofluorescence analysis using anti-p2^gag peptide monoclonal antibodies, which recognize the nona peptide (AEAMSQVTN) derived from the N-terminus of the p2^gag peptide, and cleaved by HIV-1 PR in vitro. Treatment of CEM/LAV-1 cells with the fusion peptide also resulted in a decrease in the amount of p24^gag in the resultant viral lysate derived from the cell-free supernatant. Taken together, these data suggest that the p2^gag peptide consequently blocks the autolysis of HIV-1 virions for the conservation of viral species.