{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:09:20Z","timestamp":1792714160499,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012028","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T00:00:00Z","timestamp":1710806400000}}],"reference-count":72,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T00:00:00Z","timestamp":1709078400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI144090"],"award-info":[{"award-number":["R01AI144090"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013704","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda, Paraguay","doi-asserted-by":"publisher","award":["M0037-Fordecyt 302965"],"award-info":[{"award-number":["M0037-Fordecyt 302965"]}],"id":[{"id":"10.13039\/501100013704","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012028","type":"journal-article","created":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T18:36:30Z","timestamp":1709145390000},"page":"e1012028","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["Structure and antigenicity of the divergent human astrovirus VA1 capsid spike"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3208-0071","authenticated-orcid":true,"given":"Anisa","family":"Ghosh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2247-7435","authenticated-orcid":true,"given":"Kevin","family":"Delgado-Cunningham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3699-306X","authenticated-orcid":true,"given":"Tom\u00e1s","family":"L\u00f3pez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kassidy","family":"Green","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3130-4501","authenticated-orcid":true,"given":"Carlos F.","family":"Arias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4185-5673","authenticated-orcid":true,"given":"Rebecca M.","family":"DuBois","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,2,28]]},"reference":[{"issue":"4","key":"ppat.1012028.ref001","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1128\/CMR.00013-14","article-title":"Human Astroviruses","volume":"27","author":"A Bosch","year":"2014","journal-title":"Clin Microbiol Rev"},{"issue":"3","key":"ppat.1012028.ref002","doi-asserted-by":"crossref","first-page":"376","DOI":"10.3390\/v13030376","article-title":"Human Astroviruses: A Tale of Two Strains","volume":"13","author":"V 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