MEMBRANE-FUSION INDUCED BY THE HIV TYPE-1 FUSION PEPTIDE - MODULATIONBY FACTORS AFFECTING GLYCOPROTEIN-41 ACTIVITY AND POTENTIAL ANTI-HIV COMPOUNDS

Peptides representing a sequence of 23 amino acid residues at the N te rminus of human immunodeficiency virus type 1 (HIV-1) envelope glycopr otein gp41 bind and subsequently induce fusion of large unilamellar ve sicles (LUV), an activity presumably related to gp41 function in viral infection. These in vitro effects can be modulated by several factors that are known to affect HIV-1 infectivity and gp41-mediated virus-ce ll fusion. Peptide-induced membrane fusion but not peptide binding can be inhibited by two factors known to block gp41 activity: a polar ami no acid substitution V --> E in position 2 and the presence of the N-t erminal hexapeptide of gp41 in addition to the parent sequence. Wherea s inclusion of the alternative gp120 receptor galactosylceramide in me mbranes has virtually no effect, membrane cholesterol stimulates fusio n activity. In view of its putative physiological relevance, we have u sed the fusion activity of the peptides as a tool to evaluate the inhi bitory effect of antivirals that might target this sequence, We descri be three dissimilar effects: Amphotericin B inhibits in a cholesterol- independent way peptide-induced fusion but not binding, human serum al bumin inhibits binding and consequently fusion, and dextran sulfate (M -r 5000) does not affect either binding or fusion.