AN ANTI-HIV PEPTIDE CONSTRUCT DERIVED FROM THE CLEAVAGE REGION OF THEENV PRECURSOR ACTS ON ENV FUSOGENICITY THROUGH THE PRESENCE OF A FUNCTIONAL CLEAVAGE SEQUENCE

A 22-amino-acid-long multibranched peptide construct (CLV) derived fro m the cleavage region (KIEPLGVAPTKAKRRWQREKR*) of the human immunodef iciency virus (HIV) type-1 envelope precursor inhibits HIV infection ( Virology; 1996, 223, 406-408). We attempted to characterize its activi ty for Env expressed via a recombinant vaccinia virus (rVV): gp160 cle avage was delayed, but not impaired, in the presence of CLV (10 mu M), whereas neither Env production nor Env membrane expression was signif icantly altered. Through the synthesis of analogs, we concluded that t he presence of a cleavage sequence was required for inhibition of sync ytium formation by CLV in rVV-infected CD4(+) cell cultures: indeed, a single amino acid residue substitution (R>S) in the cleavage sites p resented by CLV abolished its activity. Other analogs allowed us to fu rther determine the region of CLV which mediates its activity. The abi lity of a radiolabeled CLV analog to enter cells was also shown. Altog ether, these data strongly suggest that CLV acts on Env fusogenicity a t least partially through interference with gp160 processing. (C) 1998 Academic Press.