V-3 loop-derived peptide SPC3 inhibits infection of CD4- and galactosylceramide(-) cells by LAV-2/B

SPC3, a synthetic multibranched peptide including the GPGRAF consensus moti f of the human immunodeficiency virus type 1 (HIV-1) gp120 V3-loop is a pot ent inhibitor of HIV infection of human CD4(+) lymphocytes, macrophages and CD4(-)/ galactosylceramide(+) human colon epithelial cells and is currentl y tested in phase II clinical trials (FDA protocol 257 A). The antiviral pr operty of SPC3 was further investigated for its ability to inhibit LAV-2/B, an HIV-2 clone with a CD4-independent tropism. SPC3 inhibited the LAV-2/B- mediated infection of B-cell line which does not express the CD4 and the ga lactosylceramide molecules on their cell surface, suggesting an SPC3-sensit ive CD4/galactosylceramide-independent pathway of viral infection in HIV su sceptible cells. The molecular mechanism of the peptide inhibition was also investigated. The data suggested that the SPC3-mediated inhibition does no t result from a direct competition between SPC3 and gp120 binding to the ce ll surface of the target cell.