Journal of Virology, May 1999, p. 3661-3671, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Génétique des Virus (ICGM-CNRS
UPR 0415)1 and Signalisation,
Received 19 October 1998/Accepted 10 February 1999
Strains of the feline immunodeficiency virus (FIV) presently under
investigation exhibit distinct patterns of in vitro tropism. In
particular, the adaptation of FIV for propagation in Crandell feline
kidney (CrFK) cells results in the selection of strains capable of
forming syncytia with cell lines of diverse species origin. The
infection of CrFK cells by CrFK-adapted strains appears to require the
chemokine receptor CXCR4 and is inhibited by its natural ligand,
stromal cell-derived factor 1
(SDF-1
). Here we found that
inhibitors of CXCR4-mediated infection by human immunodeficiency virus
type I (HIV-1), such as the bicyclam AMD3100 and short peptides derived
from the amino-terminal region of SDF-1
, also blocked infection of
CrFK by FIV. Nevertheless, we observed differences in the ranking order
of the peptides as inhibitors of FIV and HIV-1 and showed that such
differences are related to the species origin of CXCR4 and not that of
the viral envelope. These results suggest that, although the envelope
glycoproteins of FIV and HIV-1 are substantially divergent, FIV and
HIV-1 interact with CXCR4 in a highly similar manner. We have also
addressed the role of CXCR4 in the life cycle of primary isolates of
FIV. Various CXCR4 ligands inhibited infection of feline peripheral blood mononuclear cells (PBMC) by primary FIV isolates in a
concentration-dependent manner. These ligands also blocked the viral
transduction of feline PBMC by pseudotyped viral particles when
infection was mediated by the envelope glycoprotein of a primary FIV
isolate but not by the G protein of vesicular stomatitis virus,
indicating that they act at an envelope-mediated step and presumably at
viral entry. These findings strongly suggest that primary and
CrFK-adapted strains of FIV, despite disparate in vitro tropisms, share
usage of CXCR4.
*
Corresponding author. Mailing address: INSERM U 332, Institut Cochin de Génétique Moléculaire, 22 rue
Méchain, 75014 Paris, France. Phone: (33)-(0)1-40 51 64 96. Fax: (33)-(0)1-40 51 77 49. E-mail:
heveker{at}cochin.inserm.fr.
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