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dc.contributor.authorHo, Antonia
dc.contributor.authorDIAMONDS consortium
dc.contributor.authorISARIC4C investigators
dc.contributor.authorWillett, Brian J.
dc.contributor.authorBreuer, Judith
dc.contributor.authorSemple, Malcolm G.
dc.contributor.authorTurner, David
dc.contributor.authorBaillie, J. Kenneth
dc.contributor.authorThomson, Emma C.
dc.date.accessioned2023-04-18T16:30:10Z
dc.date.available2023-04-18T16:30:10Z
dc.date.issued2023-05-18
dc.identifier283996169
dc.identifiera31a9804-411e-47f9-b4a9-1c4b9b04f455
dc.identifier36996873
dc.identifier85159304324
dc.identifier.citationHo , A , DIAMONDS consortium , ISARIC4C investigators , Willett , B J , Breuer , J , Semple , M G , Turner , D , Baillie , J K & Thomson , E C 2023 , ' Adeno-associated virus 2 infection in children with non-A-E hepatitis ' , Nature , vol. 617 , pp. 555-563 . https://doi.org/10.1038/s41586-023-05948-2en
dc.identifier.issn0028-0836
dc.identifier.otherORCID: /0000-0002-4958-2166/work/132764933
dc.identifier.urihttps://hdl.handle.net/10023/27426
dc.descriptionFunding: The work was funded by Public Health Scotland, the National Institute for Health Research (NIHR; award CO-CIN-01) and the Medical Research Council (MRC; grants MR/X010252/1, MC_UU_1201412, MC_UU_12018/12, MC_PC_19059, MC_PC_19025 & MC_PC_22004). DIAMONDS is funded by the European Union Horizon 2020 programme; grant 848196). MP acknowledges funding support from the Wellcome Trust (206369/Z/17/Z). MGS gratefully acknowledges funding support from The Pandemic Institute, Liverpool and the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool, and United Kingdom Health Security Agency (United KingdomHSA). JKB gratefully acknowledges funding support from a Wellcome Trust Senior Research Fellowship (223164/Z/21/Z), and MC_PC_20029, Sepsis Research (Fiona Elizabeth Agnew Trust), a BBSRC Institute Strategic Programme Grant to the Roslin Institute (BB/P013732/1, BB/P013759/1), and the United Kingdom Intensive Care Society.en
dc.description.abstractAn outbreak of acute hepatitis of unknown aetiology in children was reported in Scotland in April 20221 and has now been identified in 35 countries2. Several recent studies have suggested an association with human adenovirus (HAdV), a virus not commonly associated with hepatitis. Here we report a detailed case-control investigation and find an association between adeno-associated virus (AAV2) infection and host genetics in disease susceptibility. Using next-generation sequencing (NGS), reverse transcription-polymerase chain reaction (RT-PCR), serology and in situ hybridisation (ISH), we detected recent infection with AAV2 in the plasma and liver samples of 26/32 (81%) hepatitis cases versus 5/74 (7%) of controls. Further, AAV2 was detected within ballooned hepatocytes alongside a prominent T cell infiltrate in liver biopsies. In keeping with a CD4+ T-cell-mediated immune pathology, the Human Leucocyte Antigen (HLA) class II DRB1*04:01 allele was identified in 25/27 cases (93%), compared with a background frequency of 10/64 (16%; p=5.49 x 10-12). In summary, we report an outbreak of acute paediatric hepatitis associated with AAV2 infection (most likely acquired as a coinfection with HAdV which is required as a "helper virus" to support AAV2 replication) and HLA class II-related disease susceptibility.
dc.format.extent37060308
dc.language.isoeng
dc.relation.ispartofNatureen
dc.subjectRA0421 Public health. Hygiene. Preventive Medicineen
dc.subjectRJ Pediatricsen
dc.subjectDASen
dc.subjectSDG 3 - Good Health and Well-beingen
dc.subjectMCCen
dc.subject.lccRA0421en
dc.subject.lccRJen
dc.titleAdeno-associated virus 2 infection in children with non-A-E hepatitisen
dc.typeJournal articleen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.contributor.institutionUniversity of St Andrews. St Andrews Bioinformatics Uniten
dc.contributor.institutionUniversity of St Andrews. Infection and Global Health Divisionen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.identifier.doi10.1038/s41586-023-05948-2
dc.description.statusPeer revieweden


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