Article Metrics


Online attention

A structure-based rationale for sialic acid independent host-cell entry of Sosuga virus

DOI: 10.1073/pnas.1906717116 DOI Help

Authors: Alice J. Stelfox (Wellcome Centre for Human Genetics, University of Oxford) , Thomas A. Bowden (Wellcome Centre for Human Genetics, University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Proceedings Of The National Academy Of Sciences , VOL 10

State: Published (Approved)
Published: October 2019
Diamond Proposal Number(s): 14744

Open Access Open Access

Abstract: The bat-borne paramyxovirus, Sosuga virus (SosV), is one of many paramyxoviruses recently identified and classified within the newly established genus Pararubulavirus, family Paramyxoviridae. The envelope surface of SosV presents a receptor-binding protein (RBP), SosV-RBP, which facilitates host-cell attachment and entry. Unlike closely related hemagglutinin neuraminidase RBPs from other genera of the Paramyxoviridae, SosV-RBP and other pararubulavirus RBPs lack many of the stringently conserved residues required for sialic acid recognition and hydrolysis. We determined the crystal structure of the globular head region of SosV-RBP, revealing that while the glycoprotein presents a classical paramyxoviral six-bladed β-propeller fold and structurally classifies in close proximity to paramyxoviral RBPs with hemagglutinin-neuraminidase (HN) functionality, it presents a receptor-binding face incongruent with sialic acid recognition. Hemadsorption and neuraminidase activity analysis confirms the limited capacity of SosV-RBP to interact with sialic acid in vitro and indicates that SosV-RBP undergoes a nonclassical route of host-cell entry. The close overall structural conservation of SosV-RBP with other classical HN RBPs supports a model by which pararubulaviruses only recently diverged from sialic acid binding functionality.

Journal Keywords: virus–host interaction; viral attachment; paramyxovirus; structure; glycoprotein

Subject Areas: Biology and Bio-materials

Instruments: I04-Macromolecular Crystallography