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Structural and Mechanistic Insights into the Tropism of Epstein-Barr Virus

  • Mohl, Britta S. (Department of Microbiology and Immunology, The Feinberg School of Medicine, Northwestern University) ;
  • Chen, Jia (Department of Microbiology and Immunology, The Feinberg School of Medicine, Northwestern University) ;
  • Sathiyamoorthy, Karthik (Department of Structural Biology, Stanford University School of Medicine) ;
  • Jardetzky, Theodore S. (Department of Structural Biology, Stanford University School of Medicine) ;
  • Longnecker, Richard (Department of Microbiology and Immunology, The Feinberg School of Medicine, Northwestern University)
  • Received : 2016.03.23
  • Accepted : 2016.03.26
  • Published : 2016.04.30

Abstract

Epstein-Barr virus (EBV) is the prototypical ${\gamma}$-herpesvirus and an obligate human pathogen that infects mainly epithelial cells and B cells, which can result in malignancies. EBV infects these target cells by fusing with the viral and cellular lipid bilayer membranes using multiple viral factors and host receptor(s) thus exhibiting a unique complexity in its entry machinery. To enter epithelial cells, EBV requires minimally the conserved core fusion machinery comprised of the glycoproteins gH/gL acting as the receptor-binding complex and gB as the fusogen. EBV can enter B cells using gp42, which binds tightly to gH/gL and interacts with host HLA class II, activating fusion. Previously, we published the individual crystal structures of EBV entry factors, such as gH/gL and gp42, the EBV/host receptor complex, gp42/HLA-DR1, and the fusion protein EBV gB in a postfusion conformation, which allowed us to identify structural determinants and regions critical for receptor-binding and membrane fusion. Recently, we reported different low resolution models of the EBV B cell entry triggering complex (gHgL/gp42/HLA class II) in "open" and "closed" states based on negative-stain single particle electron microscopy, which provide further mechanistic insights. This review summarizes the current knowledge of these key players in EBV entry and how their structures impact receptor-binding and the triggering of gB-mediated fusion.

Keywords

entry;Epstein-Barr virus;fusion;herpesvirus;tropism

Acknowledgement

Supported by : National Institute of Allergy and Infectious Diseases, National Cancer Institute, Deutsche Forschungsgemeinschaft DFG, Chicago Biomedical Consortium

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