Human Cytomegalovirus Glycoproteins gB and gH/gL Mediate Epithelial Cell-Cell Fusion When Expressed either in cis or in trans
- 1 December 2008
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 82 (23), 11837-11850
- https://doi.org/10.1128/jvi.01623-08
Abstract
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.Keywords
This publication has 58 references indexed in Scilit:
- HCMV gH/gL/UL128–131 interferes with virus entry into epithelial cells: Evidence for cell type-specific receptorsProceedings of the National Academy of Sciences of the United States of America, 2008
- UL74 of Human Cytomegalovirus Contributes to Virus Release by Promoting Secondary Envelopment of VirionsJournal of Virology, 2008
- PILRα Is a Herpes Simplex Virus-1 Entry Coreceptor That Associates with Glycoprotein BCell, 2008
- Characterization of the Human Cytomegalovirus gH/gL/UL128-131 Complex That Mediates Entry into Epithelial and Endothelial CellsJournal of Virology, 2008
- Bimolecular complementation reveals that glycoproteins gB and gH/gL of herpes simplex virus interact with each other during cell fusionProceedings of the National Academy of Sciences of the United States of America, 2007
- Acceleration of allograft failure by cytomegalovirusCurrent Opinion in Immunology, 2007
- Epidermal Growth Factor Receptor Is Not Required for Human Cytomegalovirus Entry or SignalingJournal of Virology, 2007
- Herpes simplex virus glycoproteins gB and gH function in fusion between the virion envelope and the outer nuclear membraneProceedings of the National Academy of Sciences of the United States of America, 2007
- Herpes simplex virus type 1 mediates fusion through a hemifusion intermediate by sequential activity of glycoproteins D, H, L, and BProceedings of the National Academy of Sciences of the United States of America, 2007
- Soluble Epstein-Barr Virus Glycoproteins gH, gL, and gp42 Form a 1:1:1 Stable Complex That Acts Like Soluble gp42 in B-Cell Fusion but Not in Epithelial Cell FusionJournal of Virology, 2006