Structure and antigenicity of the divergent human astrovirus VA1 capsid spike.
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,...
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Language: | English |
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Public Library of Science (PLoS)
2024-02-01
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Series: | PLoS Pathogens |
Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1012028&type=printable |
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author | Anisa Ghosh Kevin Delgado-Cunningham Tomás López Kassidy Green Carlos F Arias Rebecca M DuBois |
author_facet | Anisa Ghosh Kevin Delgado-Cunningham Tomás López Kassidy Green Carlos F Arias Rebecca M DuBois |
author_sort | Anisa Ghosh |
collection | DOAJ |
description | 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. |
first_indexed | 2024-04-24T20:14:59Z |
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id | doaj.art-2a9fa5ec51c945f39836c21f7305fa5d |
institution | Directory Open Access Journal |
issn | 1553-7366 1553-7374 |
language | English |
last_indexed | 2024-04-24T20:14:59Z |
publishDate | 2024-02-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS Pathogens |
spelling | doaj.art-2a9fa5ec51c945f39836c21f7305fa5d2024-03-23T05:30:44ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742024-02-01202e101202810.1371/journal.ppat.1012028Structure and antigenicity of the divergent human astrovirus VA1 capsid spike.Anisa GhoshKevin Delgado-CunninghamTomás LópezKassidy GreenCarlos F AriasRebecca M DuBoisHuman 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.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1012028&type=printable |
spellingShingle | Anisa Ghosh Kevin Delgado-Cunningham Tomás López Kassidy Green Carlos F Arias Rebecca M DuBois Structure and antigenicity of the divergent human astrovirus VA1 capsid spike. PLoS Pathogens |
title | Structure and antigenicity of the divergent human astrovirus VA1 capsid spike. |
title_full | Structure and antigenicity of the divergent human astrovirus VA1 capsid spike. |
title_fullStr | Structure and antigenicity of the divergent human astrovirus VA1 capsid spike. |
title_full_unstemmed | Structure and antigenicity of the divergent human astrovirus VA1 capsid spike. |
title_short | Structure and antigenicity of the divergent human astrovirus VA1 capsid spike. |
title_sort | structure and antigenicity of the divergent human astrovirus va1 capsid spike |
url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1012028&type=printable |
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