Structure and antigenicity of the divergent human astrovirus VA1 capsid spike.

Autor: Ghosh A; Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, California, United States of America., Delgado-Cunningham K; Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, California, United States of America., López T; Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico., Green K; Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, California, United States of America., Arias CF; Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico., DuBois RM; Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, California, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2024 Feb 28; Vol. 20 (2), pp. e1012028. Date of Electronic Publication: 2024 Feb 28 (Print Publication: 2024).
DOI: 10.1371/journal.ppat.1012028
Abstrakt: Human astrovirus (HAstV) is a known cause of viral gastroenteritis in children worldwide, but HAstV can cause also severe and systemic infections in immunocompromised patients. There are three clades of HAstV: classical, MLB, and VA/HMO. While all three clades are found in gastrointestinal samples, HAstV-VA/HMO is the main clade associated with meningitis and encephalitis in immunocompromised patients. To understand how the HAstV-VA/HMO can infect the central nervous system, we investigated its sequence-divergent capsid spike, which functions in cell attachment and may influence viral tropism. Here we report the high-resolution crystal structures of the HAstV-VA1 capsid spike from strains isolated from patients with gastrointestinal and neuronal disease. The HAstV-VA1 spike forms a dimer and shares a core beta-barrel structure with other astrovirus capsid spikes but is otherwise strikingly different, suggesting that HAstV-VA1 may utilize a different cell receptor, and an infection competition assay supports this hypothesis. Furthermore, by mapping the capsid protease cleavage site onto the structure, the maturation and assembly of the HAstV-VA1 capsid is revealed. Finally, comparison of gastrointestinal and neuronal HAstV-VA1 sequences, structures, and antigenicity suggests that neuronal HAstV-VA1 strains may have acquired immune escape mutations. Overall, our studies on the HAstV-VA1 capsid spike lay a foundation to further investigate the biology of HAstV-VA/HMO and to develop vaccines and therapeutics targeting it.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Ghosh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje