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PMID:21880752

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Citation

Vanarsdall, AL, Chase, MC and Johnson, DC (2011) Human cytomegalovirus glycoprotein gO complexes with gH/gL, promoting interference with viral entry into human fibroblasts but not entry into epithelial cells. J. Virol. 85:11638-45

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.

Links

PubMed PMC3209304 Online version:10.1128/JVI.05659-11

Keywords

Cells, Cultured; Cytomegalovirus/physiology; Epithelial Cells/virology; Fibroblasts/virology; Humans; Membrane Glycoproteins/metabolism; Protein Binding; Protein Multimerization; Viral Envelope Proteins/metabolism; Viral Proteins/metabolism; Virus Internalization

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HCMVM:GO

involved_in

GO:0046597: negative regulation of viral entry into host cell

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HCMVM:GO

GO:0046597: negative regulation of viral entry into host cell

ECO:0000315:

P

The coexpression of gO with gH/gL substantially increases interference in human fibroblasts compared with gH/gL alone and that gH/gL/gO does not interfere in epithelial cells. Evidence for this claim is demonstrated in Figure 1.

complete
CACAO 6568


See also

References

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