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Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus
Published on: October 7, 2011
Human cytomegalovirus glycoprotein H/glycoprotein L complex modulates fusion-from-without
R S Milne1, D A Paterson, J C Booth
1Department of Medical Microbiology, St George's Hospital Medical School, London, UK.
Insights
Human cytomegalovirus (HCMV) glycoprotein H/glycoprotein L (gH/gL) complexes are essential for viral fusion. Surface-expressed gH/gL enhances HCMV-induced cell-to-cell fusion, but is not intrinsically fusogenic.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- Herpesvirus fusion relies on glycoprotein H/glycoprotein L (gH/gL) complexes.
- Neutralizing monoclonal antibodies (MAb) against gH inhibit human cytomegalovirus (HCMV) fusion.
- The fusogenic properties of HCMV gH/gL require further investigation.
Purpose of the Study:
- To investigate the role of HCMV gH/gL in cell fusion.
- To determine if surface-expressed gH/gL is intrinsically fusogenic.
- To assess the contribution of cell surface gH/gL to HCMV-mediated fusion.
Main Methods:
- Utilized neutralizing monoclonal antibodies (MAb) against HCMV gH.
- Employed defective recombinant adenovirus vectors for gH/gL expression.
- Assessed fusion-from-without in human embryonic fibroblasts and U373 astrocytoma cells.
- Investigated cell-to-cell fusion upon HCMV superinfection of cells expressing gH/gL.
Main Results:
- Neutralizing gH-specific MAb inhibited HCMV-induced fusion-from-without.
- No fusion was observed in cells expressing gH/gL via adenovirus vectors alone.
- Cells expressing gH/gL showed enhanced cell-to-cell fusion when superinfected with HCMV.
- Surface-expressed gH/gL is not intrinsically fusogenic but enhances fusion initiated by other viral components.
Conclusions:
- HCMV gH/gL complexes are critical for viral entry and cell fusion.
- Cell surface-expressed gH/gL potentiates HCMV-mediated membrane fusion.
- gH/gL acts as an enhancer of fusion rather than an initiator under these experimental conditions.
Abstract:
Glycoprotein H/glycoprotein L (gH/gL) complexes of herpesviruses are required for fusion of infecting virions with host cell membranes. In human cytomegalovirus (HCMV), neutralizing monoclonal antibodies (MAb) specific for gH inhibit the transfer of a fluorescent probe to the host cell from labelled virus particles. In similar fashion, in the present study, neutralizing gH-specific MAb inhibited HCMV-induced fusion-from-without in monolayers of both human embryonic fibroblasts and continuous astrocytoma cells (U373). No fusion was detected in cells co-infected with defective recombinant adenovirus vectors that elicited high-level expression of gH and gL, indicating that surface-expressed gH was not intrinsically fusogenic. However, when such cells were superinfected with HCMV that gave fusion-from-without, the resulting cell-to-cell fusion was considerably enhanced. Thus, under our experimental conditions, gH/gL on the cell surface functioned to increase membrane fusion once this was initiated by other components in the virus envelope.
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