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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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Autores principales: Ali, Hashim, Lulla, Aleksei, Nicholson, Alex S., Hankinson, Jack, Wignall-Fleming, Elizabeth B., O’Connor, Rhian L., Vu, Diem-Lan, Graham, Stephen C., Deane, Janet E., Guix, Susana, Lulla, Valeria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10374088/
https://www.ncbi.nlm.nih.gov/pubmed/37459343
http://dx.doi.org/10.1371/journal.pbio.3001815
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author Ali, Hashim
Lulla, Aleksei
Nicholson, Alex S.
Hankinson, Jack
Wignall-Fleming, Elizabeth B.
O’Connor, Rhian L.
Vu, Diem-Lan
Graham, Stephen C.
Deane, Janet E.
Guix, Susana
Lulla, Valeria
author_facet Ali, Hashim
Lulla, Aleksei
Nicholson, Alex S.
Hankinson, Jack
Wignall-Fleming, Elizabeth B.
O’Connor, Rhian L.
Vu, Diem-Lan
Graham, Stephen C.
Deane, Janet E.
Guix, Susana
Lulla, Valeria
author_sort Ali, Hashim
collection PubMed
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.
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spelling pubmed-103740882023-07-28 Attenuation hotspots in neurotropic human astroviruses Ali, Hashim Lulla, Aleksei Nicholson, Alex S. Hankinson, Jack Wignall-Fleming, Elizabeth B. O’Connor, Rhian L. Vu, Diem-Lan Graham, Stephen C. Deane, Janet E. Guix, Susana Lulla, Valeria PLoS Biol Methods and Resources 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. Public Library of Science 2023-07-17 /pmc/articles/PMC10374088/ /pubmed/37459343 http://dx.doi.org/10.1371/journal.pbio.3001815 Text en © 2023 Ali et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Methods and Resources
Ali, Hashim
Lulla, Aleksei
Nicholson, Alex S.
Hankinson, Jack
Wignall-Fleming, Elizabeth B.
O’Connor, Rhian L.
Vu, Diem-Lan
Graham, Stephen C.
Deane, Janet E.
Guix, Susana
Lulla, Valeria
Attenuation hotspots in neurotropic human astroviruses
title Attenuation hotspots in neurotropic human astroviruses
title_full Attenuation hotspots in neurotropic human astroviruses
title_fullStr Attenuation hotspots in neurotropic human astroviruses
title_full_unstemmed Attenuation hotspots in neurotropic human astroviruses
title_short Attenuation hotspots in neurotropic human astroviruses
title_sort attenuation hotspots in neurotropic human astroviruses
topic Methods and Resources
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10374088/
https://www.ncbi.nlm.nih.gov/pubmed/37459343
http://dx.doi.org/10.1371/journal.pbio.3001815
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