Human cytomegalovirus glycoprotein H/glycoprotein L complex modulates fusion-from-without.
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.
Milne
R S
RS
Department of Medical Microbiology, St George's Hospital Medical School, London, UK.
Paterson
D A
DA
Booth
J C
JC
D000256:Adenoviridae / Q000235:genetics; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001483:Base Sequence; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D003609:Dactinomycin / Q000494:pharmacology; D003673:Defective Viruses / Q000235:genetics; D006801:Humans; D008561:Membrane Fusion / Q000187:drug effects / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D017931:DNA Primers; D014759:Viral Envelope Proteins; C071440:glycoprotein H, Cytomegalovirus; C499358:glycoprotein H, Human cytomegalovirus; C077407:glycoprotein L, Human herpesvirus 1; D003609:Dactinomycin