SPC3, an anti-HIV peptide construct derived from the viral envelope, bindsand enters HIV target cells

SPC3 is a peptide construct (eight branches of the GPGRAF motif) derived fr om the consensus sequence present at the apex of the third variable domain of the human immunodeficiency virus (HIV) envelope (Env). It presents a pot ent anti-HIV activity and is currently tested in phase II clinical trials ( FDA protocol 257A). Its mode of action remains unclear. It was thought that SPC3 exerts its effect both during HIV interaction with CD4(+) cells but a lso through interference either with a post-binding event or with Env proce ssing. Accordingly, SPC3 was supposed to be able to bind and to enter CD4() cells. In this work, we addressed these points. SPC3 was found to interac t with CD4(+) cell membrane with a K-0.5, Value in the range of 500 nM. The binding of SPC3 to CD4(+) cells involves its interaction with a cell membr ane associated protein which is pronase sensitive and different from CD4. T his interaction was similar from 2 to 37 degrees C. The maximum binding occ urred at acidic pH whereas the interaction was inhibited in alkaline condit ions. We observed also that SPC3 was internalized rapidly into the cells - the maximal intracell amount was reached within 30 min - where it remained stable for at least 24 h. Altogether, these data suggest that SPC3 can exer t its antiviral activity via interference with events occurring at the cell surface but also into the target cell. (C) 1998 European Peptide Society a nd John Wiley & Sons, Ltd.