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Epstein-Barr virus gH/gL has multiple sites of vulnerability for virus neutralization and fusion inhibition

  1. Author:
    Chen, Wei-Hung
    Kim, JungHyun
    Bu, Wei
    Board, Nathan L
    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

  2. Author Address

    Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA., Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Vaccine Research Center Electron Microscopy Unit, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., Clinical Services Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: gjoyce@eidresearch.org., Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: jcohen@niaid.nih.gov.,
    1. Year: 2022
    2. Date: Nov 8
    3. Epub Date: 2022 10 26
  2. Journal: Immunity
    1. 55
    2. 11
    3. Pages: 2135-2148
  4. Type of Article: Article
  1. 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. Published by Elsevier Inc.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.immuni.2022.10.003
  3. PMID: 36306784
  4. PMCID: PMC9815946
  5. View record in Web of Science®
  6. WOS: 000919605800004
  7. PII : S1074-7613(22)00544-1

Library Notes

  1. Fiscal Year: FY2022-2023
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