Ho, Antonia;
Orton, Richard;
Tayler, Rachel;
Asamaphan, Patawee;
Herder, Vanessa;
Davis, Chris;
Tong, Lily;
... Thomson, Emma C; + view all
(2023)
Adeno-associated virus 2 infection in children with non-A-E hepatitis.
Nature
10.1038/s41586-023-05948-2.
(In press).
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Abstract
An 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.
| Type: | Article |
|---|---|
| Title: | Adeno-associated virus 2 infection in children with non-A-E hepatitis |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41586-023-05948-2 |
| Publisher version: | https://doi.org/10.1038/s41586-023-05948-2 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. - For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10168114 |
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