dc.contributor.author
Morfopoulou, Sofia
dc.contributor.author
Buddle, Sarah
dc.contributor.author
Torres Montaguth, Oscar Enrique
dc.contributor.author
Atkinson, Laura
dc.contributor.author
Guerra-Assunção, José Afonso
dc.contributor.author
Moradi Marjaneh, Mahdi
dc.contributor.author
Zennezini Chiozzi, Riccardo
dc.contributor.author
Storey, Nathaniel
dc.contributor.author
Kaufer, Benedikt B.
dc.contributor.author
Reich, Jana
dc.date.accessioned
2023-10-19T09:24:27Z
dc.date.available
2023-10-19T09:24:27Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/41199
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-40920
dc.description.abstract
Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children.
en
dc.format.extent
29 Seiten
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
Clinical microbiology
en
dc.subject
Paediatric research
en
dc.subject.ddc
500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie::570 Biowissenschaften; Biologie
dc.title
Genomic investigations of unexplained acute hepatitis in children
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.doi
10.1038/s41586-023-06003-w
dcterms.bibliographicCitation.journaltitle
Nature
dcterms.bibliographicCitation.number
7961
dcterms.bibliographicCitation.pagestart
564
dcterms.bibliographicCitation.pageend
573
dcterms.bibliographicCitation.volume
617
dcterms.bibliographicCitation.url
https://doi.org/10.1038/s41586-023-06003-w
refubium.affiliation
Veterinärmedizin
refubium.affiliation.other
Institut für Virologie
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.eissn
1476-4687
refubium.resourceType.provider
WoS-Alert