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http://dx.doi.org/10.14348/molcells.2016.0066

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)
Publication Information
Molecules and Cells / v.39, no.4, 2016 , pp. 286-291 More about this Journal
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;
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