Functional Characterization of Epstein-Barr Virus gH/gL Glycoprotein Complex in Fusion Jasmina Omerović Epstein-Barr virus (EBV) is a human gamma-herpesvirus that primarily infects B cells and epithelial cells. While the glycoproteins required for entry into these two cell types differ, the gH/gL glycoprotein complex is essential for entry into both epithelial and B cells. Analysis of gH protein sequences from three gamma-herpesviruses: EBV, marmoset and rhesus, revealed a potential coiled-coil

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... domain in the N-terminus. Four leucines located in this region in EBV gH were replaced with alanines by site-directed mutagenesis and analyzed for cell-cell membrane fusion with B cells and epithelial cells. Reduction in fusion activity was observed for mutants containing L65A and/or L69A mutations, while substitutions in L55 and L74 enhanced the fusion activity of the mutant gH/gL complexes with both cell types. All of the mutants displayed levels of cell surface expression similar to those of wild-type gH and interacted with gL and gp42. The observation that a conservative mutation of leucine to alanine in the N-terminus of EBV gH results in fusion defective mutant gH/gL complexes is striking and points to an important role for this region in EBV-mediated membrane fusion with B cells and epithelial cells. Furthermore, even though the gH/gL complex is conserved within the herpesvirus family, its exact role in entry and mechanism of fusion are not known yet. To understand more about the FIGURE 29: The Proposed Model of EBV Fusion Complex Formation