Human Cytomegalovirus gH/gL Forms a Stable Complex with the Fusion Protein gB in Virions

PLoS Pathogens

Adam L. Vanarsdall¹  Paul W. Howard¹  David C. Johnson¹  Todd W. Wisner¹ 

[1] Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, Oregon, United States of America

关键词: Virions;    Cell fusion;    Membrane fusion;    Human cytomegalovirus;    Antibodies;    Serum proteins;    Glycoproteins;    Protein extraction;   

DOI  :  10.1371/journal.ppat.1005564

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY