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J Virol, August 1998, p. 6389-6397, Vol. 72, No. 8
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

Olivier Pleskoff,dagger Carole Tréboute, and Marc Alizon*

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.

* 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.

dagger Present address: Laboratoire de Virologie, Ecole Normale Supérieure, Lyon, France.

J Virol, August 1998, p. 6389-6397, Vol. 72, No. 8
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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