Attenuation hotspots in neurotropic human astroviruses
During the last decade, the detection of neurotropic astroviruses has increased dramatically. The MLB genogroup of astroviruses represents a genetically distinct group of zoonotic astroviruses associated with gastroenteritis and severe neurological complications in young children, the immunocompromi...
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| Veröffentlicht in: | PLoS biology 2023-07, Vol.21 (7), p.e3001815 |
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| creator | Ali, Hashim Lulla, Aleksei Nicholson, Alex S Hankinson, Jacqueline Wignall-Fleming, Elizabeth B O'Connor, Rhian L Vu, Diem-Lan Graham, Stephen C Deane, Janet E Guix, Susana Lulla, Valeria |
| description | During the last decade, the detection of neurotropic astroviruses has increased dramatically. The MLB genogroup of astroviruses represents a genetically distinct group of zoonotic astroviruses associated with gastroenteritis and severe neurological complications in young children, the immunocompromised, and the elderly. Using different virus evolution approaches, we identified dispensable regions in the 3' end of the capsid-coding region responsible for attenuation of MLB astroviruses in susceptible cell lines. To create recombinant viruses with identified deletions, MLB reverse genetics (RG) and replicon systems were developed. Recombinant truncated MLB viruses resulted in imbalanced RNA synthesis and strong attenuation in iPSC-derived neuronal cultures confirming the location of neurotropism determinants. This approach can be used for the development of vaccine candidates using attenuated astroviruses that infect humans, livestock animals, and poultry. |
| doi_str_mv | 10.1371/journal.pbio.3001815 |
| format | Article |
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The MLB genogroup of astroviruses represents a genetically distinct group of zoonotic astroviruses associated with gastroenteritis and severe neurological complications in young children, the immunocompromised, and the elderly. Using different virus evolution approaches, we identified dispensable regions in the 3' end of the capsid-coding region responsible for attenuation of MLB astroviruses in susceptible cell lines. To create recombinant viruses with identified deletions, MLB reverse genetics (RG) and replicon systems were developed. Recombinant truncated MLB viruses resulted in imbalanced RNA synthesis and strong attenuation in iPSC-derived neuronal cultures confirming the location of neurotropism determinants. This approach can be used for the development of vaccine candidates using attenuated astroviruses that infect humans, livestock animals, and poultry.</description><identifier>ISSN: 1545-7885</identifier><identifier>ISSN: 1544-9173</identifier><identifier>EISSN: 1545-7885</identifier><identifier>DOI: 10.1371/journal.pbio.3001815</identifier><identifier>PMID: 37459343</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aged ; Animals ; Astroviridae Infections - diagnosis ; Astroviridae Infections - veterinary ; Attenuation ; Biology and life sciences ; Capsid ; Capsid Proteins - genetics ; Cell culture ; Cell lines ; Child ; Child, Preschool ; Coding ; Complications ; Evolution ; Gastroenteritis ; Genetics ; Genomes ; Health aspects ; Humans ; Infections ; Livestock ; Mamastrovirus - genetics ; Medicine and Health Sciences ; Methods and Resources ; Neurological complications ; Neurotrophic functions ; Neurotropism ; Pathogenesis ; Phylogeny ; Proteins ; RNA polymerase ; RNA viruses ; Transcription ; Vaccines ; Viruses</subject><ispartof>PLoS biology, 2023-07, Vol.21 (7), p.e3001815</ispartof><rights>Copyright: © 2023 Ali 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.</rights><rights>COPYRIGHT 2023 Public Library of Science</rights><rights>2023 Ali et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 Ali et al 2023 Ali et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c696t-a47847e055988d2ac002f0f90ff6795e5f5e22567b963d7899c0d63796655d663</citedby><cites>FETCH-LOGICAL-c696t-a47847e055988d2ac002f0f90ff6795e5f5e22567b963d7899c0d63796655d663</cites><orcidid>0000-0002-6605-0727</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10374088/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10374088/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37459343$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ali, Hashim</creatorcontrib><creatorcontrib>Lulla, Aleksei</creatorcontrib><creatorcontrib>Nicholson, Alex S</creatorcontrib><creatorcontrib>Hankinson, Jacqueline</creatorcontrib><creatorcontrib>Wignall-Fleming, Elizabeth B</creatorcontrib><creatorcontrib>O'Connor, Rhian L</creatorcontrib><creatorcontrib>Vu, Diem-Lan</creatorcontrib><creatorcontrib>Graham, Stephen C</creatorcontrib><creatorcontrib>Deane, Janet E</creatorcontrib><creatorcontrib>Guix, Susana</creatorcontrib><creatorcontrib>Lulla, Valeria</creatorcontrib><title>Attenuation hotspots in neurotropic human astroviruses</title><title>PLoS biology</title><addtitle>PLoS Biol</addtitle><description>During the last decade, the detection of neurotropic astroviruses has increased dramatically. The MLB genogroup of astroviruses represents a genetically distinct group of zoonotic astroviruses associated with gastroenteritis and severe neurological complications in young children, the immunocompromised, and the elderly. Using different virus evolution approaches, we identified dispensable regions in the 3' end of the capsid-coding region responsible for attenuation of MLB astroviruses in susceptible cell lines. To create recombinant viruses with identified deletions, MLB reverse genetics (RG) and replicon systems were developed. Recombinant truncated MLB viruses resulted in imbalanced RNA synthesis and strong attenuation in iPSC-derived neuronal cultures confirming the location of neurotropism determinants. This approach can be used for the development of vaccine candidates using attenuated astroviruses that infect humans, livestock animals, and poultry.</description><subject>Aged</subject><subject>Animals</subject><subject>Astroviridae Infections - diagnosis</subject><subject>Astroviridae Infections - veterinary</subject><subject>Attenuation</subject><subject>Biology and life sciences</subject><subject>Capsid</subject><subject>Capsid Proteins - genetics</subject><subject>Cell culture</subject><subject>Cell lines</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Coding</subject><subject>Complications</subject><subject>Evolution</subject><subject>Gastroenteritis</subject><subject>Genetics</subject><subject>Genomes</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Infections</subject><subject>Livestock</subject><subject>Mamastrovirus - genetics</subject><subject>Medicine and Health Sciences</subject><subject>Methods and Resources</subject><subject>Neurological complications</subject><subject>Neurotrophic functions</subject><subject>Neurotropism</subject><subject>Pathogenesis</subject><subject>Phylogeny</subject><subject>Proteins</subject><subject>RNA polymerase</subject><subject>RNA viruses</subject><subject>Transcription</subject><subject>Vaccines</subject><subject>Viruses</subject><issn>1545-7885</issn><issn>1544-9173</issn><issn>1545-7885</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqVkltvFCEUxydGY2v1GxjdxBd92BWG4fZkNo2XTRqbeHslDJddNjMwBabRby_rTpuO6YOGEA7wO384l6p6DsEKIgrf7sMYvexWQ-vCCgEAGcQPqlOIG7ykjOGHd-yT6klKewDqmtfscXWCaIM5atBpRdY5Gz_K7IJf7EJOQ5kL5xfejDHkGAanFruxl34hU9leuzgmk55Wj6zsknk2rWfV9w_vv51_Wl5cftycry-WinCSl7KhrKEGYMwZ07VU5QsWWA6sJZRjgy02dY0JbTlBmjLOFdAEUU4IxpoQdFa9POoOXUhiCjmJmmHIMQMIFGJzJHSQezFE18v4SwTpxJ-DELdCxuxUZ4RhkrWNQVwy2lhNi40xbjWypmYU6aL1bnptbHujlfE5ym4mOr_xbie24VpAUDIKGCsKryeFGK5Gk7LoXVKm66Q3YTx8HPEaI8hwQV_9hd4f3kRtZYnAeVtqItVBVKwpAaApJYWFWt1DlaFN71TwxrpyPnN4M3MoTDY_81aOKYnN1y__wX7-d_byx5xtjqyKIaVo7G2iIRCHFr9JiDi0uJhavLi9uFukW6ebnka_AURs9MU</recordid><startdate>20230717</startdate><enddate>20230717</enddate><creator>Ali, Hashim</creator><creator>Lulla, Aleksei</creator><creator>Nicholson, Alex S</creator><creator>Hankinson, Jacqueline</creator><creator>Wignall-Fleming, Elizabeth B</creator><creator>O'Connor, Rhian L</creator><creator>Vu, Diem-Lan</creator><creator>Graham, Stephen C</creator><creator>Deane, Janet E</creator><creator>Guix, Susana</creator><creator>Lulla, Valeria</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISN</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PATMY</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><scope>CZG</scope><orcidid>https://orcid.org/0000-0002-6605-0727</orcidid></search><sort><creationdate>20230717</creationdate><title>Attenuation hotspots in neurotropic human astroviruses</title><author>Ali, Hashim ; Lulla, Aleksei ; Nicholson, Alex S ; Hankinson, Jacqueline ; Wignall-Fleming, Elizabeth B ; O'Connor, Rhian L ; Vu, Diem-Lan ; Graham, Stephen C ; Deane, Janet E ; Guix, Susana ; Lulla, Valeria</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c696t-a47847e055988d2ac002f0f90ff6795e5f5e22567b963d7899c0d63796655d663</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Aged</topic><topic>Animals</topic><topic>Astroviridae Infections - 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The MLB genogroup of astroviruses represents a genetically distinct group of zoonotic astroviruses associated with gastroenteritis and severe neurological complications in young children, the immunocompromised, and the elderly. Using different virus evolution approaches, we identified dispensable regions in the 3' end of the capsid-coding region responsible for attenuation of MLB astroviruses in susceptible cell lines. To create recombinant viruses with identified deletions, MLB reverse genetics (RG) and replicon systems were developed. Recombinant truncated MLB viruses resulted in imbalanced RNA synthesis and strong attenuation in iPSC-derived neuronal cultures confirming the location of neurotropism determinants. This approach can be used for the development of vaccine candidates using attenuated astroviruses that infect humans, livestock animals, and poultry.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>37459343</pmid><doi>10.1371/journal.pbio.3001815</doi><orcidid>https://orcid.org/0000-0002-6605-0727</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Animals Astroviridae Infections - diagnosis Astroviridae Infections - veterinary Attenuation Biology and life sciences Capsid Capsid Proteins - genetics Cell culture Cell lines Child Child, Preschool Coding Complications Evolution Gastroenteritis Genetics Genomes Health aspects Humans Infections Livestock Mamastrovirus - genetics Medicine and Health Sciences Methods and Resources Neurological complications Neurotrophic functions Neurotropism Pathogenesis Phylogeny Proteins RNA polymerase RNA viruses Transcription Vaccines Viruses |
| title | Attenuation hotspots in neurotropic human astroviruses |
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