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Rotavirus VP4 Epitope of a Broadly Neutralizing Human Antibody Defined by Its Structure Bound with an Attenuated-Strain Virion

Year: 2022
Type: article
Abstract: Rotavirus live-attenuated vaccines generate broadly heterotypic protection, and B-cells isolated from adults encode antibodies that are broadly protective in mice. Determining the structural and mechanistic basis of broad protection can contribute to understanding the current limitations of vaccine efficacy in developing countries. The structure of an attenuated human rotavirus isolate (CDC-9) bound with the Fab fragment of a broadly heterotypic protective antibody shows that protection is probably due to inhibition of the conformational transition in the viral spike protein (VP4) critical for viral penetration, rather than to inhibition of receptor binding. A comparison of structures of CDC-9 virus particles at two stages of serial passaging supports a proposed mechanism for initial steps in rotavirus membrane penetration.
DOI: 10.1128/jvi.00627-22
Authors: Simon Jenni, Zongli Li, Yuhuan Wang, Theresa Bessey, Eric N. Salgado, Aaron G. Schmidt, Harry B. Greenberg, Baoming Jiang, Stephen C. Harrison
Institutions: Harvard University, Howard Hughes Medical Institute, Centers for Disease Control and Prevention, Boston Children's Hospital, Ragon Institute of MGH, MIT and Harvard, Massachusetts Institute of Technology, VA Palo Alto Health Care System, Stanford Medicine, Stanford University
Language: English
Field: Medicine
Open Access status: green
Awards: G1127461966, Regulation of Rotavirus Replication, Virulence, and Host Range Restriction by the Innate Immune System, G3242670473, G4327804863, G6108659733, Regulation of Rotavirus Replication and Virulence by the Innate and Adaptive Immune Systems, Structure and Assembly of Viruses, Structure and Assembly of Viruses
OpenAlex ID: W4289844279
FWCI: 2.074
Cites: 54
Cited by: 20
Related to: 10