The Effect of Metalloendopeptidase-F on HIV-1

Abstract

Objective: To study the effect of Metalloendopeptidase-F (MEP-F), a major active ingredient of the anti-inflammatory drug Pronase, on HIV-1 in vitro.
Materials and Methods: HIV-1/LAI and AD8 stock viruses were treated with various concentrations of MEP-F and then incubated in PHA-activated normal human peripheral blood mononuclear cells (PBMC) for 5 days. PBMC or PHA-blast cells were treated with MEP-F either before or after infection with HIV-1. The cells were cultured for 5 days after infection. HIV-1 replication was evaluated by p24 antigen measurement using ELISA. The effect of MEP-F on cell surface antigens was analyzed by fluorescence-activated cell sorter (FACS).
Results: Treatment of HIV-1/LAI and AD8 with MEP-F resulted in a decreased viral infectivity. When PHA-blast cells infected with HIV/LAI were cultured in the presence of MEP-F, a dose-related inhibition of HIV-1p24 production was observed. Furthermore, when PBMC were treated with MEP-F prior to infection with HIV-1/LAI and then cultured in the medium with PHA added, the production of HIV-1 p24 antigen was significantly reduced. FACS analysis of cell-surface markers on MEP-F-treated PBMC revealed a remarkable decline of CD4 and CXCR4 levels expressed on CD3⁺ T cells.
Conclusion: It is suggested that MEP-F is effective against HIV-1 infection by acting on the surface proteins of both the virus and the host cell.