INHIBITION OF INFECTIOUS HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 PARTICLEFORMATION BY GAG PROTEIN-DERIVED PEPTIDES

Sequential overlapping Gag protein-derived oligopeptides of human immu nodeficiency virus type 1 (HIV-1) 22 to 24 amino acids long, were synt hesized and tested in vitro for antiviral activity. Two synthetic pept ides, one derived from the matrix protein p17 (NPGLLETSEGCRQ, amino ac ids 47 to 59) and one located in the capsid protein p24 (PAATLEEMMTA, amino acids 339 to 349) inhibited the production of infectious virus w hen added to HIV-1-infected cultures when used in the range of 20 to 2 00 mu g/ml. As shown by thin section electron microscopy, peptide trea tment resulted in the release of immature, deformed virus particles su ggesting that the two peptides interfered with assembly and maturation . Other Gag protein-derived oligopeptides had little or no influence o n virus production. To characterize further the functionally active re gions we synthesized peptide derivatives with three consecutive amino acids substituted by alanine; they did not cause inhibition. Therefore the regions responsible for inhibition were located between amino aci ds 50 to 61 in p17, and 342 to 350 in p24. These observations might le ad to the development of a new antiviral strategy affecting the late s tage of virus replication.