title: Human Cytomegalovirus gH/gL Forms a Stable Complex with the Fusion Protein gB in Virions.
abstract: Human cytomegalovirus (HCMV) is a ubiquitous virus that is a major pathogen in newborns and immunocompromised or immunosuppressed patients. HCMV infects a wide variety of cell types using distinct entry pathways that involve different forms of the gH/gL glycoprotein: gH/gL/gO and gH/gL/UL128-131 as well as the viral fusion glycoprotein, gB. However, the minimal or core fusion machinery (sufficient for cell-cell fusion) is just gH/gL and gB. Here, we demonstrate that HCMV gB and gH/gL form a stable complex early after their synthesis and in the absence of other viral proteins. gH/gL can interact with gB mutants that are unable to mediate cell-cell fusion. gB-gH/gL complexes included as much as 16-50% of the total gH/gL in HCMV virus particles. In contrast, only small amounts of gH/gL/gO and gH/gL/UL128-131 complexes were found associated with gB. All herpesviruses express gB and gH/gL molecules and most models describing herpesvirus entry suggest that gH/gL interacts with gB to mediate membrane fusion, although there is no direct evidence for this. For herpes simplex virus (HSV-1) it has been suggested that after receptor binding gH/gL binds to gB either just before, or coincident with membrane fusion. Therefore, our results have major implications for these models, demonstrating that HCMV gB and gH/gL forms stable gB-gH/gL complexes that are incorporated virions without receptor binding or membrane fusion. Moreover, our data is the best support to date for the proposal that gH/gL interacts with gB.
authors.affiliation: Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Adam L
authors.initials: AL
authors.lastname: Vanarsdall
authors.affiliation: Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Howard
authors.affiliation: Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Todd W
authors.initials: TW
authors.lastname: Wisner
authors.affiliation: Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: David C
authors.initials: DC
authors.lastname: Johnson
mesh_terms: D015153:Blotting, Western; D003587:Cytomegalovirus / Q000378:metabolism / Q000472:pathogenicity*; D003586:Cytomegalovirus Infections / Q000821:virology*; D006801:Humans; D047468:Immunoprecipitation; D014760:Viral Fusion Proteins / Q000378:metabolism*; D014771:Virion / Q000378:metabolism / Q000472:pathogenicity*; D053586:Virus Internalization
chemical_list: D014760:Viral Fusion Proteins