INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION AND SYNCYTIUM FORMATION IN HUMAN-CELLS BY V3 LOOP SYNTHETIC PEPTIDES FROM GP120

Because V3 loop-specific antibodies have been shown to inhibit human i mmunodeficiency virus type 1 (HIV-1) infection of human cells and beca use specific mutations in the V3 loop render the virus ineffective for infection and syncytium formation, we tested the anti-HIV effects of V3 loop peptides from different HIV-1 strains. We obtained evidence th at V3 loop synthetic peptides of 8 to 15 amino acids at nanogram conce ntrations efficiently blocked HIV-1 IIIB infection of several human T- cell lines and of freshly prepared normal human T cells. More importan tly, syncytium formation by three different primary clinical HIV isola tes was inhibited by the V3 loop peptide from HIV-1 IIIB at a concentr ation Of 1 mug/ml. Concentrations of V3 peptides up to 50 mug/ml were not toxic to any of the human cells studied. Additionally, V3 peptides incubated in normal human serum or plasma exhibited biological and ph ysical stability for up to 24 h. Taken together, these results suggest that the V3 loop peptides have medical utility as therapeutic reagent s to either prevent HIV-1 infection in humans or reduce the spread of virus infection in HIV-infected individuals. These findings are especi ally significant because a number of reports in the literature indicat e that the V3 loop region in gp120 Plays an important role in the init ial stages of HIV-1 infection of cells.