HCMV gH/gL/UL128-131 interferes with virus entry into epithelial cells: Evidence for cell type-specific receptors

Brent J. Ryckman, Marie C. Chase, David C. Johnson

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Human cytomegalovirus (HCMV) forms two different membrane protein complexes, gH/gL/gO and gH/gL/UL128/UL130/UL131, that function in different cell types. gH/gL/gO appears to be important for HCMV entry into or spread between fibroblasts, processes that occur at neutral pH. We demonstrated that HCMV entry into epithelial and endothelial cells requires gH/gL/UL128-131 and involves endocytosis and low pH. A complex of all five HCMV proteins, gH, gL, UL128, UL130, and UL131, is the functionally important mediator of this entry pathway into epithelial/endothelial cells. Here, we report that expression of gH/gL/UL128-131 in ARPE-19 epithelial cells causes the cells to be resistant to HCMV infection. Another HCMV glycoprotein, gB, did not interfere, and expression of all five gH/gL/UL128-131 proteins was required for this interference. gH/gL/UL128-131 interference was at the stage of virus entry into cells rather than the initial adsorption onto cell surfaces or after-entry defects. By contrast, expression of gH/gL/ UL128-131 in primary human fibroblasts did not block HCMV infection. Previously, interference by retrovirus and herpes-simplex-virus entry mediators resulted from sequestration or obstruction of receptors. We concluded that epithelial cells express gH/ gL/UL128-131 receptors that mediate HCMV entry. Fibroblasts either lack the gH/gL/UL128-131 receptors, the receptors are more numerous, or fibroblasts express other functional receptors.

Original languageEnglish
Pages (from-to)14118-14123
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number37
StatePublished - Sep 16 2008


  • HCMV glycoproteins
  • Receptor interference


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