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J Virol, August 1998, p. 6389-6397, Vol. 72, No. 8
INSERM U.332, Institut Cochin de
Génétique Moléculaire, 75014 Paris, France
Received 11 February 1998/Accepted 28 April 1998
The human cytomegalovirus (CMV) US28 gene encodes a
functional CC chemokine receptor. However, this activity was observed in cells transfected to express US28 and might not correspond to the
actual role of the protein in the CMV life cycle. Expression of US28
allows human immunodeficiency virus type 1 (HIV-1) entry into certain
CD4+ cells and their fusion with cells expressing HIV-1
envelope (Env) proteins. Such properties were initially reported for
the cellular chemokine receptors CCR5 and CXCR4, which behave as
CD4-associated HIV-1 coreceptors. We found that coexpression of
US28 and either CXCR4 or CCR5 in CD4+ cells resulted
in enhanced synctium formation with HIV-1 Env+ cells. This
positive effect of US28 on cell fusion seems to be distinct from its
HIV-1 coreceptor activity. Indeed, enhancement of cell fusion was also
observed when US28 was expressed on the HIV-1 Env+ cells
instead of an CD4+ target cells. Furthermore, US28
could enhance cell fusion mediated by other viral proteins, in
particular, the G protein of vesicular stomatitis virus (VSV-G). The
HIV-1 coreceptor and fusion-enhancing activities could be affected by
mutations in different domains of US28. The fusion-enhancing activity
of US28 seems to be cell type dependent. Indeed, cells
coexpressing VSV-G and US28 fused more efficiently with human, simian,
or feline target cells, while US28 had no apparent effect on fusion
with the three mouse or rat cell lines tested. The positive effect of
US28 on cell fusion might therefore require its interaction with a
cell-specific factor. We discuss a possible role for US28 in the fusion
of the CMV envelope with target cells and CMV entry.
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
The Cytomegalovirus-Encoded Chemokine Receptor US28 Can
Enhance Cell-Cell Fusion Mediated by Different Viral
Proteins

*
Corresponding author. Mailing address: INSERM U.332,
Institut Cochin de Génétique Moléculaire, 22 rue
Méchain, 75014 Paris, France. Phone: 33-1-40 51 64 86. Fax:
33-1-40 51 77 49. E-mail: alizon{at}cochin.inserm.fr.
Present address: Laboratoire de Virologie, Ecole Normale
Supérieure, Lyon, France.
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