Rationally designed chemokine-based toxin targeting the viral G protein-coupled receptor US28 potently inhibits cytomegalovirus infection in vivo

Authors

• Katja Spiess, INAGEN Aps.
• Mads G. Jeppesen, INAGEN Aps.
• Mikkel Malmgaard-Clausen, INAGEN Aps.
• Karen Krzywkowski, INAGEN Aps.
• Kalpana Dulal, Rutgers - The State University of New Jersey, Newark
• Tong Cheng, Xiamen University
• Gertrud M. Hjortø, University of Copenhagen
• Olav Larsen, University of Copenhagen
• John S. Burg, Stanford University
• Michael A. Jarvis, School of Biomedical Sciences
• K. Christopher Garcia, Stanford University
• Hua Zhu, Rutgers - The State University of New Jersey, Newark
• Thomas N. Kledal, INAGEN Aps.
• Mette M. Rosenkilde, University of Copenhagen

ORCID

• Michael A. Jarvis: 0000-0002-0124-4061

Abstract

Significance All drugs currently used for the clinical treatment of human cytomegalovirus (HCMV) infection are associated with considerable adverse side effects and with the development of drug resistance that results in therapy failure. Here we describe a novel, rationally designed fusion toxin protein (FTP)-based strategy to target HCMV on the basis of its virally expressed G protein-coupled receptor (US28) and cognate chemokine ligand. Viral G protein-coupled receptors are expressed by a number of other clinically important viruses. We suggest that FTP-based molecules targeting virally expressed 7TM receptors may represent a new class of drugs amenable for development against complex viral pathogens.

DOI Link

10.1073/pnas.1509392112

Publication Date

2015-07-07

Publication Title

Proceedings of the National Academy of Sciences

Volume

112

Issue

27

ISSN

0027-8424

Embargo Period

9999-12-31

First Page

8427

Last Page

8432

Recommended Citation

Spiess, K., Jeppesen, M., Malmgaard-Clausen, M., Krzywkowski, K., Dulal, K., Cheng, T., Hjortø, G., Larsen, O., Burg, J., Jarvis, M., Garcia, K., Zhu, H., Kledal, T., & Rosenkilde, M. (2015) 'Rationally designed chemokine-based toxin targeting the viral G protein-coupled receptor US28 potently inhibits cytomegalovirus infection in vivo', Proceedings of the National Academy of Sciences, 112(27), pp. 8427-8432. Available at: 10.1073/pnas.1509392112