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SPC 3 , an anti‐HIV peptide construct derived from the viral envelope, binds and enters HIV target cells
Author(s) -
Barbouche Rym,
Miquelis Raymond,
Sabatier JeanMarc,
Fenouillet Emmanuel
Publication year - 1998
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/(sici)1099-1387(199812)4:8<479::aid-psc167>3.0.co;2-i
Subject(s) - human immunodeficiency virus (hiv) , peptide , virology , viral envelope , construct (python library) , envelope (radar) , chemistry , lentivirus , biology , microbiology and biotechnology , biochemistry , viral disease , computer science , telecommunications , radar , programming language
Abstract SPC 3 is a peptide construct (eight branches of the GPGRAF motif) derived from the consensus sequence present at the apex of the third variable domain of the human immunodeficiency virus (HIV) envelope (Env). It presents a potent 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 SPC 3 exerts its effect both during HIV interaction with CD4 + cells but also through interference either with a post‐binding event or with Env processing. Accordingly, SPC 3 was supposed to be able to bind and to enter CD4 + cells. In this work, we addressed these points. SPC 3 was found to interact with CD4 + cell membrane with a K 0.5 value in the range of 500 n m . The binding of SPC 3 to CD4 + cells involves its interaction with a cell membrane associated protein which is pronase sensitive and different from CD4. This interaction was similar from 2 to 37°C. The maximum binding occurred at acidic pH whereas the interaction was inhibited in alkaline conditions. We observed also that SPC 3 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 SPC 3 can exert its antiviral activity via interference with events occurring at the cell surface but also into the target cell. © 1998 European Peptide Society and John Wiley & Sons, Ltd.