title: Human cytomegalovirus glycoprotein gO complexes with gH/gL, promoting interference with viral entry into human fibroblasts but not entry into epithelial cells.
abstract: A complex of five human cytomegalovirus virus (HCMV) proteins, gH, gL, UL128, UL130, and UL131 (gH/gL/UL128-131), is essential for virus entry into epithelial cells. We previously showed that gH/gL/UL128-131 expressed in epithelial cells interferes with subsequent HCMV entry into cells. There was no interference with only gH/gL or gB. We concluded that the expression of gH/gL/UL128-131 causes a mislocalization or downregulation of epithelial cell proteins that HCMV requires for entry. In contrast, gH/gL/UL128-131 expression in fibroblasts did not produce interference, suggesting a different mechanism for entry. Here, we show that the coexpression of another HCMV glycoprotein, gO, with gH/gL in human fibroblasts interferes with HCMV entry into fibroblasts but not epithelial cells. However, the coexpression of gO with gH/gL did not increase the cell surface expression level of gH/gL and did not enhance cell-cell fusion, a process that depends upon cell surface gH/gL. Instead, gO promoted the export of gH/gL from the endoplasmic reticulum (ER) and the accumulation of gH/gL in the trans-Golgi network. Thus, interference with gH/gL or gH/gL/gO, i.e., the mislocalization or blocking of entry mediators, occurs in cytoplasmic membranes and not in cell surface membranes of fibroblasts. Together, the results provide additional support for our hypotheses that epithelial cells express putative gH/gL/UL128-1331 receptors important for HCMV entry and that fibroblasts express distinct gH/gL receptors.
authors: L-220, Department of Microbiology and Immunology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA.
authors: Adam L
authors: AL
authors: Vanarsdall
authors: Marie C
authors: MC
authors: Chase
authors: David C
authors: DC
authors: Johnson
mesh_terms: D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000502:physiology*; D004847:Epithelial Cells / Q000821:virology; D005347:Fibroblasts / Q000821:virology; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: D008562:Membrane Glycoproteins; C077406:UL115 protein, Human herpesvirus 5; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C499358:glycoprotein H, Human cytomegalovirus; C439068:glycoprotein O, cytomegalovirus