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Journal of Virology, November 2001, p. 10472-10478, Vol. 75, No. 21
Biomedical Research Centre, Ninewells
Hospital and Medical School, University of Dundee, Dundee DD1 9SY,
Scotland
Received 19 January 2001/Accepted 30 July 2001
Entry of human T-cell leukemia virus type 1 (HTLV-1) into cells is
mediated by the viral envelope glycoproteins gp46 and gp21. The gp46 surface glycoprotein binds to a poorly
characterized cell surface receptor, thereby promoting the
gp21-dependent fusion of the viral and cellular membranes.
Interestingly, a synthetic peptide (P-197) simulating amino acids 197 to 216 of gp46 strongly inhibits envelope-dependent membrane fusion
with Molt-4 target cells. It has been suggested that this peptide acts
by competitively binding to Hsc70, a putative cellular receptor for
HTLV-1. We now demonstrate that P-197 inhibits membrane fusion
among diverse HTLV-1-permissive target cells. Importantly, most of
these cells lack detectable levels of Hsc70, indicating that P-197
inhibits membrane fusion by a mechanism that is Hsc70 independent. We
now suggest that competition for primary receptor
binding is unlikely to account for the inhibitory activity of P-197.
Understanding the mechanism by which P-197 functions may reveal
concepts of general relevance to antiretroviral chemotherapy.
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.21.10472-10478.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
The Synthetic Peptide P-197 Inhibits Human T-Cell Leukemia Virus
Type 1 Envelope-Mediated Syncytium Formation by a Mechanism That Is
Independent of Hsc70
*
Corresponding author. Mailing address: Biomedical
Research Centre, Ninewells Hospital and Medical School, Level 5, University of Dundee, Dundee DD1 9SY, Scotland. Phone: 44 (0)1382
660111, ext. 33513. Fax: 44 (0)1382 669993. E-mail:
brighty{at}icrf.icnet.uk.
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