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  • Review Article
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Review Article

Virally encoded 7TM receptors

Oncogene volume 20, pages 1582–1593 (2001)Cite this article

Abstract

A number of herpes- and poxviruses encode 7TM G-protein coupled receptors most of which clearly are derived from their host chemokine system as well as induce high expression of certain 7TM receptors in the infected cells. The receptors appear to be exploited by the virus for either immune evasion, cellular reprogramming, tissue targeting or for cell entry. Through their efficient evolutionary machinery and through in vivo selection performed directly on the human cellular and molecular targets, virus have been able to optimize the encoded receptors for distinct pharmacological profiles to help in various parts of the viral life cyclus. Most of the receptors encoded by human pathogenic virus are still orphan receptors, i.e. the endogenous ligand is unknown. In the few cases where it has been possible to characterize these receptors pharmacologically, they have been found to bind a broad spectrum of either CC chemokines, US28 from human cytomegalovirus, or CXC chemokines, ORF74 from human herpesvirus 8. Nevertheless, US28 has been specifically optimized for recognition of the membrane bound chemokine, fractalkine, conceivably involved in cell–cell transfer of virus; whereas ORF74 among the endogenous CXC chemokines has selected angiogenic chemokines as agonists and angiostatic/modulatory chemokines as inverse agonists. ORF74 possess substantial cell-transforming properties and signals with high constitutive activity through the phospholipase C and MAP kinase pathways. Interestingly, transgenic expression of this single gene in certain lymphocyte cell lineages leads to the development of lesions which are remarkably similar to Kaposi's sarcoma, a human herpesvirus 8 associated disease. Thus, this and other virally encoded 7TM receptors appear to be attractive future drug targets.

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Acknowledgements

Special thanks to François Talabot and Timothy Wells, Serono Research Group, Geneva, Switzerland for generation of basic information of the dendrograms presented in Figure 1. This study was supported by grants from the Danish Medical Research Council, the Danish Cancer Association, the Lundbeck Foundation (MM Rosenkilde, HR Lüttichau and TW Schwartz) and by an EMBO Fellowship (M Waldhoer).

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Authors and Affiliations

  1. Department of Pharmacology, Laboratory for Molecular Pharmacology, Panum Institute, DK-2200, Denmark

    Mette M Rosenkilde, Maria Waldhoer, Hans R Lüttichau & Thue W Schwartz

  2. Department for Infectious Diseases, Rigshospitalet, Copenhagen, DK-2100, Denmark

    Hans R Lüttichau

  3. 7TM-Pharma A/S, Rønnegade 2, Copenhagen, DK-2100, Denmark

    Thue W Schwartz

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  1. Mette M Rosenkilde
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Rosenkilde, M., Waldhoer, M., Lüttichau, H. et al. Virally encoded 7TM receptors. Oncogene 20, 1582–1593 (2001). https://doi.org/10.1038/sj.onc.1204191

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