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Human Cytomegalovirus-Encoded G Protein-Coupled Receptor UL33 Facilitates Virus Dissemination via the Extracellular and Cell-to-Cell Route.
Viruses. 2020 May 30; 12(6)V

Abstract

Human cytomegalovirus (HCMV) encodes four G protein-coupled receptor (GPCR) homologs. Three of these receptors, UL78, US27 and US28, are known for their roles in HCMV dissemination and latency. Despite importance of its rodent orthologs for viral replication and pathogenesis, such a function is not reported for the HCMV-encoded GPCR UL33. Using the clinical HCMV strain Merlin, we show that UL33 facilitates both cell-associated and cell-free virus transmission. A UL33-deficient virus derivative revealed retarded virus spread, formation of less and smaller plaques, and reduced extracellular progeny during multi-cycle growth analysis in fibroblast cultures compared to parental virus. The growth of UL33-revertant, US28-deficient, and US28-revertant viruses were similar to parental virus under multistep growth conditions. UL33- and US28-deficient Merlin viruses impaired cell-associated virus spread to a similar degree. Thus, the growth defect displayed by the UL33-deficient virus but not the US28-deficient virus reflects UL33's contribution to extracellular transmission. In conclusion, UL33 facilitates cell-associated and cell-free spread of the clinical HCMV strain Merlin in fibroblast cultures.

Authors+Show Affiliations

Amsterdam Institute for Molecular and Life Sciences (AIMMS), Division of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands.Amsterdam Institute for Molecular and Life Sciences (AIMMS), Division of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands.Amsterdam Institute for Molecular and Life Sciences (AIMMS), Division of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands.Amsterdam Institute for Molecular and Life Sciences (AIMMS), Division of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands.Amsterdam Institute for Molecular and Life Sciences (AIMMS), Division of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands.Amsterdam Institute for Molecular and Life Sciences (AIMMS), Division of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands.Amsterdam Institute for Molecular and Life Sciences (AIMMS), Division of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32486172

Citation

van Senten, Jeffrey R., et al. "Human Cytomegalovirus-Encoded G Protein-Coupled Receptor UL33 Facilitates Virus Dissemination Via the Extracellular and Cell-to-Cell Route." Viruses, vol. 12, no. 6, 2020.
van Senten JR, Bebelman MP, van Gasselt P, et al. Human Cytomegalovirus-Encoded G Protein-Coupled Receptor UL33 Facilitates Virus Dissemination via the Extracellular and Cell-to-Cell Route. Viruses. 2020;12(6).
van Senten, J. R., Bebelman, M. P., van Gasselt, P., Bergkamp, N. D., van den Bor, J., Siderius, M., & Smit, M. J. (2020). Human Cytomegalovirus-Encoded G Protein-Coupled Receptor UL33 Facilitates Virus Dissemination via the Extracellular and Cell-to-Cell Route. Viruses, 12(6). https://doi.org/10.3390/v12060594
van Senten JR, et al. Human Cytomegalovirus-Encoded G Protein-Coupled Receptor UL33 Facilitates Virus Dissemination Via the Extracellular and Cell-to-Cell Route. Viruses. 2020 May 30;12(6) PubMed PMID: 32486172.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human Cytomegalovirus-Encoded G Protein-Coupled Receptor UL33 Facilitates Virus Dissemination via the Extracellular and Cell-to-Cell Route. AU - van Senten,Jeffrey R, AU - Bebelman,Maarten P, AU - van Gasselt,Puck, AU - Bergkamp,Nick D, AU - van den Bor,Jelle, AU - Siderius,Marco, AU - Smit,Martine J, Y1 - 2020/05/30/ PY - 2020/05/12/received PY - 2020/05/25/revised PY - 2020/05/27/accepted PY - 2020/6/4/entrez PY - 2020/6/4/pubmed PY - 2020/6/4/medline KW - 7TM receptor KW - G protein-coupled receptor (GPCR) KW - HCMV KW - chemokine receptor KW - cytomegalovirus JF - Viruses JO - Viruses VL - 12 IS - 6 N2 - Human cytomegalovirus (HCMV) encodes four G protein-coupled receptor (GPCR) homologs. Three of these receptors, UL78, US27 and US28, are known for their roles in HCMV dissemination and latency. Despite importance of its rodent orthologs for viral replication and pathogenesis, such a function is not reported for the HCMV-encoded GPCR UL33. Using the clinical HCMV strain Merlin, we show that UL33 facilitates both cell-associated and cell-free virus transmission. A UL33-deficient virus derivative revealed retarded virus spread, formation of less and smaller plaques, and reduced extracellular progeny during multi-cycle growth analysis in fibroblast cultures compared to parental virus. The growth of UL33-revertant, US28-deficient, and US28-revertant viruses were similar to parental virus under multistep growth conditions. UL33- and US28-deficient Merlin viruses impaired cell-associated virus spread to a similar degree. Thus, the growth defect displayed by the UL33-deficient virus but not the US28-deficient virus reflects UL33's contribution to extracellular transmission. In conclusion, UL33 facilitates cell-associated and cell-free spread of the clinical HCMV strain Merlin in fibroblast cultures. SN - 1999-4915 UR - https://www.unboundmedicine.com/medline/citation/32486172/Human_Cytomegalovirus-Encoded_G_Protein-Coupled_Receptor_UL33_Facilitates_Virus_Dissemination_via_the_Extracellular_and_Cell-to-Cell_Route L2 - https://www.mdpi.com/resolver?pii=v12060594 DB - PRIME DP - Unbound Medicine ER -
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