9DQX

Structure of western equine encephalitis virus CBA87 VLP

Summary for 9DQX

• Entry DOI: 10.2210/pdb9dqx/pdb
• EMDB information: 47117
• Descriptor: Structural polyprotein, Capsid protein, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: western equine encephalitis virus, weev, virus like particles, virus like particle
• Biological source: Western equine encephalitis virus; More
• Total number of polymer chains: 12
• Total formula weight: 443735.71

Authors

Abraham, J.,Fan, X.,Li, W. (deposition date: 2024-09-24, release date: 2025-03-26, Last modification date: 2026-04-08)

Primary citation

Fan, X.,Li, W.,Oros, J.,Plante, J.A.,Mitchell, B.M.,Plung, J.S.,Basu, H.,Nagappan-Chettiar, S.,Boeckers, J.M.,Tjang, L.V.,Mann, C.J.,Brusic, V.,Buck, T.K.,Varnum, H.,Yang, P.,Malcolm, L.M.,Choi, S.Y.,de Souza, W.M.,Chiu, I.M.,Umemori, H.,Weaver, S.C.,Plante, K.S.,Abraham, J.
Molecular basis for shifted receptor recognition by an encephalitic arbovirus.
Cell, 188:2957-2973.e28, 2025

PubMed Abstract: Western equine encephalitis virus (WEEV) is an arbovirus that historically caused large outbreaks of encephalitis throughout the Americas. WEEV binds protocadherin 10 (PCDH10) as a receptor, and highly virulent ancestral WEEV strains also bind low-density lipoprotein receptor (LDLR)-related proteins. As WEEV declined as a human pathogen in North America over the past century, isolates have lost the ability to bind mammalian receptors while still recognizing avian receptors. To explain shifts in receptor dependencies and assess the risk of WEEV re-emergence, we determined cryoelectron microscopy structures of WEEV bound to human PCDH10, avian PCDH10, and human very-low-density lipoprotein receptor (VLDLR). We show that one to three E2 glycoprotein substitutions are sufficient for a nonpathogenic strain to regain the ability to bind mammalian receptors. A soluble VLDLR fragment protects mice from lethal challenge by a virulent ancestral WEEV strain. Because WEEV recently re-emerged in South America after decades of inactivity, our findings have important implications for outbreak preparedness.

PubMed: 40187345
DOI: 10.1016/j.cell.2025.03.029

Experimental method

ELECTRON MICROSCOPY (3.4 Å)