Rationally designed chemokine-based toxin targeting the viral G protein-coupled receptor US28 potently inhibits cytomegalovirus infection in vivo
Authors
K. Christopher Garcia, Stanford University
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
Hua Zhu, Rutgers - The State University of New Jersey, Newark
Thomas N. Kledal, INAGEN Aps.
Mette M. Rosenkilde, University of Copenhagen
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.
Publication Date
2015-07-07
Publication Title
Proceedings of the National Academy of Sciences
Embargo Period
9999-12-31
Recommended Citation
Garcia, K.,
Spiess, K.,
Jeppesen, M.,
Malmgaard-Clausen, M.,
Krzywkowski, K.,
Dulal, K.,
Cheng, T.,
Hjortø, G.,
Larsen, O.,
Burg, J.,
Jarvis, M.,
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
This item is under embargo until 31 December 9999
10.1073/pnas.1509392112" data-hide-no-mentions="true">
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