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

Katja Spiess; Mads G. Jeppesen; Mikkel Malmgaard-Clausen; Karen Krzywkowski; Kalpana Dulal; Tong Cheng; Gertrud M. Hjortø; Olav Larsen; John S. Burg; Michael A. Jarvis; K. Christopher Garcia; Hua Zhu; Thomas N. Kledal; Mette M. Rosenkilde

doi:10.1073/pnas.1509392112

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

Katja Spiess, Mads G. Jeppesen, Mikkel Malmgaard-Clausen, Karen Krzywkowski, Kalpana Dulal, Tong Cheng, Gertrud M. Hjortø, Olav Larsen, John S. Burg, Michael A. Jarvis, K. Christopher Garcia^*, Hua Zhu, Thomas N. Kledal, Mette M. Rosenkilde

^*Corresponding author for this work

School of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	8427-8432
Number of pages	0
Journal	Proceedings of the National Academy of Sciences
Volume	112
Issue number	27
Early online date	15 Jun 2015
DOIs	https://doi.org/10.1073/pnas.1509392112
Publication status	Published - 7 Jul 2015

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Spiess, K., Jeppesen, M. G., Malmgaard-Clausen, M., Krzywkowski, K., Dulal, K., Cheng, T., Hjortø, G. M., Larsen, O., Burg, J. S., Jarvis, M. A., Garcia, K. C., Zhu, H., Kledal, T. N., & Rosenkilde, M. 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), 8427-8432. https://doi.org/10.1073/pnas.1509392112

@article{29bce7e038614ded893670cf96e6c503,

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

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.",

author = "Katja Spiess and Jeppesen, \{Mads G.\} and Mikkel Malmgaard-Clausen and Karen Krzywkowski and Kalpana Dulal and Tong Cheng and Hjort{\o}, \{Gertrud M.\} and Olav Larsen and Burg, \{John S.\} and Jarvis, \{Michael A.\} and Garcia, \{K. Christopher\} and Hua Zhu and Kledal, \{Thomas N.\} and Rosenkilde, \{Mette M.\}",

year = "2015",

month = jul,

day = "7",

doi = "10.1073/pnas.1509392112",

language = "English",

volume = "112",

pages = "8427--8432",

journal = "Proceedings of the National Academy of Sciences",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "27",

}

Spiess, K, Jeppesen, MG, Malmgaard-Clausen, M, Krzywkowski, K, Dulal, K, Cheng, T, Hjortø, GM, Larsen, O, Burg, JS, Jarvis, MA, Garcia, KC, Zhu, H, Kledal, TN & Rosenkilde, MM 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, vol. 112, no. 27, pp. 8427-8432. https://doi.org/10.1073/pnas.1509392112

Rationally designed chemokine-based toxin targeting the viral G protein-coupled receptor US28 potently inhibits cytomegalovirus infection in vivo. / Spiess, Katja; Jeppesen, Mads G.; Malmgaard-Clausen, Mikkel et al.
In: Proceedings of the National Academy of Sciences, Vol. 112, No. 27, 07.07.2015, p. 8427-8432.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Rationally designed chemokine-based toxin targeting the viral G protein-coupled receptor US28 potently inhibits cytomegalovirus infection in vivo

AU - Spiess, Katja

AU - Jeppesen, Mads G.

AU - Malmgaard-Clausen, Mikkel

AU - Krzywkowski, Karen

AU - Dulal, Kalpana

AU - Cheng, Tong

AU - Hjortø, Gertrud M.

AU - Larsen, Olav

AU - Burg, John S.

AU - Jarvis, Michael A.

AU - Garcia, K. Christopher

AU - Zhu, Hua

AU - Kledal, Thomas N.

AU - Rosenkilde, Mette M.

PY - 2015/7/7

Y1 - 2015/7/7

N2 - 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.

AB - 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.

UR - https://pearl.plymouth.ac.uk/bhs-research/431/

U2 - 10.1073/pnas.1509392112

DO - 10.1073/pnas.1509392112

M3 - Article

SN - 0027-8424

VL - 112

SP - 8427

EP - 8432

JO - Proceedings of the National Academy of Sciences

JF - Proceedings of the National Academy of Sciences

IS - 27

ER -

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

Abstract

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