Structure and antigenicity of the divergent human astrovirus VA1 capsid spike

Ghosh, Anisa; Delgado-Cunningham, Kevin; López, Tomás; Green, Kassidy; Arias, Carlos F.; DuBois, Rebecca M.

doi:10.1371/journal.ppat.1012028

Title: Structure and antigenicity of the divergent human astrovirus VA1 capsid spike

Journal Article · 28 February 2024 · PLoS Pathogens

DOI: https://doi.org/10.1371/journal.ppat.1012028 · OSTI ID:2471058

^[1];

^[2]; Green, Kassidy ^[1];

^[2];

^[1]

University of California, Santa Cruz, CA (United States)
Universidad Nacional Autónoma de México, Cuernavaca, Morelos (Mexico)

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.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). Advanced Light Source (ALS); Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF); National Institutes of Health (NIH); Consejo Nacional de Ciencia y Tecnología (CONACyT); W.M. Keck Foundation

Grant/Contract Number:: AC02-05CH11231; AC02-06CH11357

OSTI ID:: 2471058

Journal Information:: PLoS Pathogens, Journal Name: PLoS Pathogens Journal Issue: 2 Vol. 20; ISSN 1553-7374

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

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60 APPLIED LIFE SCIENCES
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Crystal structure
Enzyme-linked immunoassays
Microbiology
Parasitology
Recombinant proteins
Serine proteases
Viral packaging
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Title: Structure and antigenicity of the divergent human astrovirus VA1 capsid spike

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