Epstein-Barr virus gH/gL has multiple sites of vulnerability for virus neutralization and fusion inhibition. Academic Article uri icon

Overview

abstract

  • Epstein-Barr virus (EBV) is nearly ubiquitous in adults. EBV causes infectious mononucleosis and is associated with B cell lymphomas, epithelial cell malignancies, and multiple sclerosis. The EBV gH/gL glycoprotein complex facilitates fusion of virus membrane with host cells and is a target of neutralizing antibodies. Here, we examined the sites of vulnerability for virus neutralization and fusion inhibition within EBV gH/gL. We developed a panel of human monoclonal antibodies (mAbs) that targeted five distinct antigenic sites on EBV gH/gL and prevented infection of epithelial and B cells. Structural analyses using X-ray crystallography and electron microscopy revealed multiple sites of vulnerability and defined the antigenic landscape of EBV gH/gL. One mAb provided near-complete protection against viremia and lymphoma in a humanized mouse EBV challenge model. Our findings provide structural and antigenic knowledge of the viral fusion machinery, yield a potential therapeutic antibody to prevent EBV disease, and emphasize gH/gL as a target for herpesvirus vaccines and therapeutics.

authors

  • Chen, Wei-Hung
  • Kim, JungHyun
  • Bu, Wei
  • Board, Nathan
  • Tsybovsky, Yaroslav
  • Wang, Yanmei
  • Hostal, Anna
  • Andrews, Sarah F
  • Gillespie, Rebecca A
  • Choe, Misook
  • Stephens, Tyler
  • Yang, Eun Sung
  • Pegu, Amarendra
  • Peterson, Caroline E
  • Fisher, Brian E
  • Mascola, John R
  • Pittaluga, Stefania
  • McDermott, Adrian B
  • Kanekiyo, Masaru
  • Joyce, M Gordon
  • Cohen, Jeffrey I

publication date

  • October 27, 2022

Research

keywords

  • Epstein-Barr Virus Infections
  • Herpesvirus 4, Human

Identity

PubMed Central ID

  • PMC9815946

Scopus Document Identifier

  • 85141334373

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2022.10.003

PubMed ID

  • 36306784

Additional Document Info

volume

  • 55

issue

  • 11