Cytomegalovirus UL131-128 Products Promote gB Conformational Transition and gB-gH Interaction during Entry into Endothelial Cells
- 15 October 2007
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 81 (20), 11479-11488
- https://doi.org/10.1128/jvi.00788-07
Abstract
Herpesviruses use gB and gH-gL glycoproteins to execute fusion. Other virus-specific glycoproteins are required for receptor binding and fusion activation. The human cytomegalovirus (HCMV) UL131-128 proteins are essential for the infection of leukocytes, endothelial cells (ECs), and many epithelial cell lines. Here we show that UL131-128 play a role in a chain of events involving gB and gH during HCMV entry into ECs. An HCMV strain bearing the wild-type (wt) UL131-128 locus exhibited a gB transition from a protease-resistant to protease-sensitive form, a conformational change that was suppressed by a thiourea inhibitor of fusion (WY1768); in contrast, gH was susceptible to proteolysis throughout entry. Moreover, gB and gH transiently interacted, and a lipid mixing assay showed that the wt strain had carried out fusion by 60 min postinfection. However, these events were greatly altered when UL131-128-defective strains were used for infection or when there was an excess of soluble pUL128 during wt infection: the gB conformational change became WY1768 resistant, the gB-gH complex was no longer observed, and fusion was prevented. Both gB and gH in this case showed late protease resistance, related to their endocytic uptake. Our data point to the involvement of UL131-128 proteins in driving gB through a WY1768-sensitive fold transition, thus promoting a short-lived gB-gH complex and fusion; they also suggest that HCMV fuses with the EC plasma membrane and that endocytosis ensues only when the virus cannot trigger UL131-128-dependent steps.Keywords
This publication has 54 references indexed in Scilit:
- 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
- The herpesvirus glycoproteins B and H·L are sequentially recruited to the receptor-bound gD to effect membrane fusion at virus entryProceedings of the National Academy of Sciences of the United States of America, 2006
- Crystal Structure of Glycoprotein B from Herpes Simplex Virus 1Science, 2006
- Rational Development of β-Peptide Inhibitors of Human Cytomegalovirus EntryPublished by Elsevier BV ,2006
- Human Cytomegalovirus Entry into Epithelial and Endothelial Cells Depends on Genes UL128 to UL150 and Occurs by Endocytosis and Low-pH FusionJournal of Virology, 2006
- Membrane Hemifusion: Crossing a Chasm in Two LeapsCell, 2005
- Driving cells into atherosclerotic lesions– a deleterious role for viral chemokine receptors?Trends in Microbiology, 2000
- Nuclear import as a barrier to infection of human umbilical vein endothelial cells by human cytomegalovirus strain AD169Virus Research, 1998
- The Human Cytomegalovirus UL100 Gene Encodes the gC-II glycoproteins Recognized by Group 2 Monoclonal AntibodiesJournal of General Virology, 1994