Viruses 2014, 6(3), 1202-1218; doi:10.3390/v6031202
Article

Human Cytomegalovirus US28 Facilitates Cell-to-Cell Viral Dissemination

1email, 1email, 2email, 3email, 3email and 1,* email
Received: 20 January 2014; in revised form: 1 March 2014 / Accepted: 4 March 2014 / Published: 12 March 2014
(This article belongs to the Special Issue Recent CMV Research)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Human cytomegalovirus (HCMV) encodes a number of viral proteins with homology to cellular G protein-coupled receptors (GPCRs). These viral GPCRs, including US27, US28, UL33, and UL78, have been ascribed numerous functions during infection, including activating diverse cellular pathways, binding to immunomodulatory chemokines, and impacting virus dissemination. To investigate the role of US28 during virus infection, two variants of the clinical isolate TB40/E were generated: TB40/E-US28YFP expressing a C-terminal yellow fluorescent protein tag, and TB40/E-FLAGYFP in which a FLAG-YFP cassette replaces the US28 coding region. The TB40/E-US28YFP protein localized as large perinuclear fluorescent structures at late times post-infection in fibroblasts, endothelial, and epithelial cells. Interestingly, US28YFP is a non-glycosylated membrane protein throughout the course of infection. US28 appears to impact cell-to-cell spread of virus, as the DUS28 virus (TB40/E-FLAGYFP) generated a log-greater yield of extracellular progeny whose spread could be significantly neutralized in fibroblasts. Most strikingly, in epithelial cells, where dissemination of virus occurs exclusively by the cell-to-cell route, TB40/E-FLAGYFP (DUS28) displayed a significant growth defect. The data demonstrates that HCMV US28 may contribute at a late stage of the viral life cycle to cell-to-cell dissemination of virus.
Keywords: human cytomegalovirus; BAC recombineering; viral GPCR US28; virus dissemination; virus growth; membrane protein biology
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MDPI and ACS Style

Noriega, V.M.; Gardner, T.J.; Redmann, V.; Bongers, G.; Lira, S.A.; Tortorella, D. Human Cytomegalovirus US28 Facilitates Cell-to-Cell Viral Dissemination. Viruses 2014, 6, 1202-1218.

AMA Style

Noriega VM, Gardner TJ, Redmann V, Bongers G, Lira SA, Tortorella D. Human Cytomegalovirus US28 Facilitates Cell-to-Cell Viral Dissemination. Viruses. 2014; 6(3):1202-1218.

Chicago/Turabian Style

Noriega, Vanessa M.; Gardner, Thomas J.; Redmann, Veronika; Bongers, Gerold; Lira, Sergio A.; Tortorella, Domenico. 2014. "Human Cytomegalovirus US28 Facilitates Cell-to-Cell Viral Dissemination." Viruses 6, no. 3: 1202-1218.


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