Epstein-Barr Virus GH/gL Has Multiple Sites of Vulnerability for Virus Neutralization and Fusion Inhibition

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2022 Oct 28

PMID 36306784

Authors

Wei-Hung Chen

JungHyun Kim

Wei Bu

Nathan L Board

Yaroslav Tsybovsky

Yanmei Wang

Anna Hostal

Sarah F Andrews

Rebecca A Gillespie

Misook Choe

Tyler Stephens

Eun Sung Yang

Amarendra Pegu

Caroline E Peterson

Brian E Fisher

John R Mascola

Stefania Pittaluga

Adrian B McDermott

Masaru Kanekiyo

M Gordon Joyce

Jeffrey I Cohen

Affiliations

Soon will be listed here.

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.

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