ANTIMICROBIAL PEPTIDES MELITTIN AND CECROPIN INHIBIT REPLICATION OF HUMAN-IMMUNODEFICIENCY-VIRUS-1 BY SUPPRESSING VIRAL GENE-EXPRESSION

Antimicrobial peptides are effecters of innate immunity, providing the ir hosts with rapid non-specific defence against parasitic invaders. I n this report, the effects are assessed of two well-characterized anti microbial amphipathic peptides (melittin and cecropin) on human immuno deficiency virus 1 (HIV-1) replication and gene expression in acutely infected cells at subtoxic concentrations. Production of infectious, c ell-free virus was inhibited in a dose-dependent manner, with ID50 val ues in the range 0.9-1.5 mu M for melittin and 2-3 mu M for cecropin, Analysis of the effect of melittin on cell-associated virus production revealed decreased levels of Gag antigen and HIV-1 mRNAs, Transient t ransfection assays with HIV long terminal repeat (LTR)-driven reporter gene plasmids indicated that melittin has a direct suppressive effect on activity of the HIV LTR. HIV LTR activity was also reduced in huma n cells stably transfected with retroviral expression plasmids for the melittin or cecropin gene, It is concluded that antimicrobial peptide s such as melittin and cecropin are capable of inhibiting cell-associa ted production of HIV-1 by suppressing HIV-1 gene expression.