A glycoprotein B-neutralizing antibody structure at 2.8 Å uncovers a critical domain for herpesvirus fusion initiation

Year: 2020

Type: article

Abstract: Members of the Herpesviridae, including the medically important alphaherpesvirus varicella-zoster virus (VZV), induce fusion of the virion envelope with cell membranes during entry, and between cells to form polykaryocytes in infected tissues. The conserved glycoproteins, gB, gH and gL, are the core functional proteins of the herpesvirus fusion complex. gB serves as the primary fusogen via its fusion loops, but functions for the remaining gB domains remain unexplained. As a pathway for biological discovery of domain function, our approach used structure-based analysis of the viral fusogen together with a neutralizing antibody. We report here a 2.8 Å cryogenic-electron microscopy structure of native gB recovered from VZV-infected cells, in complex with a human monoclonal antibody, 93k. This high-resolution structure guided targeted mutagenesis at the gB-93k interface, providing compelling evidence that a domain spatially distant from the gB fusion loops is critical for herpesvirus fusion, revealing a potential new target for antiviral therapies.

Source: Nature Communications

DOI: 10.1038/s41467-020-17911-0

Authors: Stefan L. Oliver, Yi Xing, Dong-Hua Chen, Soung Hun Roh, Grigore D. Pintilie, David A. Bushnell, Marvin H. Sommer, Edward Yang, Andrea Carfi, Wah Chiu, Ann M. Arvin

Institutions: Stanford Medicine, Stanford University, Syros Pharmaceuticals (United States), Seoul National University, SLAC National Accelerator Laboratory, Stanford Synchrotron Radiation Lightsource

Language: English

Topic: Herpesvirus Infections and Treatments

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $5,380

Funders: U.S. Department of Health and Human Services, National Institutes of Health, University of California, San Francisco, Stanford Bio-X, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, SLAC National Accelerator Laboratory

OpenAlex ID: W3067701309