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Journal of Virology, December 2008, p. 11837-11850, Vol. 82, No. 23
0022-538X/08/$08.00+0     doi:10.1128/JVI.01623-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Human Cytomegalovirus Glycoproteins gB and gH/gL Mediate Epithelial Cell-Cell Fusion When Expressed either in cis or in trans{triangledown}

Adam L. Vanarsdall, Brent J. Ryckman, Marie C. Chase, and David C. Johnson*

Department of Molecular Microbiology and Immunology, Oregon Health and Sciences University, Portland, Oregon 97239

Received 29 July 2008/ Accepted 11 September 2008

Herpesviruses use a cascade of interactions with different cell surface molecules to gain entry into cells. In many cases, this involves binding to abundant glycosaminoglycans or integrins followed by interactions with more limited cell surface proteins, leading to fusion with cellular membranes. Human cytomegalovirus (HCMV) has the ability to infect a wide variety of human cell types in vivo. However, very little is known about which HCMV glycoproteins mediate entry into various cell types, including relevant epithelial and endothelial cells. For other herpesviruses, studies of cell-cell fusion induced by viral proteins have provided substantial information about late stages of entry. In this report, we describe the fusion of epithelial, endothelial, microglial, and fibroblast cells in which HCMV gB and gH/gL were expressed from nonreplicating adenovirus vectors. Fusion frequently involved the majority of cells, and gB and gH/gL were both necessary and sufficient for fusion, whereas no fusion occurred when either glycoprotein was omitted. Coexpression of UL128, UL130, and UL131 did not enhance fusion. We concluded that the HCMV core fusion machinery consists of gB and gH/gL. Coimmunoprecipitation indicated that HCMV gB and gH/gL can interact. Importantly, expression of gB and gH/gL in trans (gB-expressing cells mixed with other gH/gL-expressing cells) resulted in substantial fusion. We believe that this is the first description of a multicomponent viral fusion machine that can be split between cells. If gB and gH/gL must interact for fusion, then these molecules must reach across the space between apposing cells. Expression of gB and gH/gL in trans with different cell types revealed surface molecules that are required for fusion on HCMV-permissive cells but not on nonpermissive cells.

* Corresponding author. Mailing address: 6366 Basic Sciences Building, Mail Code L-220, Dept. of Molecular Microbiology and Immunology, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239. Phone: (503) 494-0658. Fax: (503) 494-6862. E-mail: johnsoda{at}ohsu.edu

{triangledown} Published ahead of print on 24 September 2008.

Journal of Virology, December 2008, p. 11837-11850, Vol. 82, No. 23
0022-538X/08/$08.00+0     doi:10.1128/JVI.01623-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Plate, A. E., Smajlovic, J., Jardetzky, T. S., Longnecker, R. (2009). Functional Analysis of Glycoprotein L (gL) from Rhesus Lymphocryptovirus in Epstein-Barr Virus-Mediated Cell Fusion Indicates a Direct Role of gL in gB-Induced Membrane Fusion. J. Virol. 83: 7678-7689 [Abstract] [Full Text]  


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