Structure-guided Mutagenesis of Henipavirus Receptor-binding Proteins Reveals Molecular Determinants of Receptor Usage and Antibody-binding Epitopes

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2024 Mar 1

PMID 38426726

Authors

Kasopefoluwa Y Oguntuyo

Griffin D Haas

Kristopher D Azarm

Christian S Stevens

Luca Brambilla

Shreyas S Kowdle

Victoria A Avanzato

Rhys Pryce

Alexander N Freiberg

Thomas A Bowden

Benhur Lee

Affiliations

Soon will be listed here.

Abstract

Importance: Hendra virus and Nipah virus (NiV) are lethal, zoonotic Henipaviruses (HNVs) that cause respiratory and neurological clinical features in humans. Since their initial outbreaks in the 1990s, several novel HNVs have been discovered worldwide, including Ghana virus. Additionally, there is serological evidence of zoonotic transmission, lending way to concerns about future outbreaks. HNV infection of cells is mediated by the receptor-binding protein (RBP) and the Fusion protein (F). The work presented here identifies NiV RBP amino acids important for the usage of ephrin-B3 (EFNB3), a receptor highly expressed in neurons and predicted to be important for neurological clinical features caused by NiV. This study also characterizes epitopes recognized by antibodies against divergent HNV RBPs. Together, this sheds insight to amino acids critical for HNV receptor usage and antibody binding, which is valuable for future studies investigating determinants of viral pathogenesis and developing antibody therapies.

Citing Articles

A monoclonal antibody targeting the Nipah virus fusion glycoprotein apex imparts protection from disease.

Avanzato V, Bushmaker T, Oguntuyo K, Yinda C, Duyvesteyn H, Stass R J Virol. 2024; 98(10):e0063824.

PMID: 39240113 PMC: 11494970. DOI: 10.1128/jvi.00638-24.

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