Adeno-associated virus 2 infection in children with non-A-E hepatitis

Ho, A. et al. (2023) Adeno-associated virus 2 infection in children with non-A-E hepatitis. Nature, 617(7961), pp. 555-563. (doi: 10.1038/s41586-023-05948-2) (PMID:36996873)

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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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:McMenamin, Dr James and Robertson, Professor David and Roy, Dr Kirsty and Baillie, Dr Kenneth and Willett, Professor Brian and Shepherd, Dr Samantha and Ho, Dr Antonia and Asamaphan, Dr Patawee and Thomson, Professor Emma and Palmarini, Professor Massimo and Tong, Dr Lily and Bradley-Stewart, Dr Amanda and Davis, Dr Chris and Evans, Clair and Pollock, Dr Louisa and Vink, Elen and Orton, Dr Richard and Herder, Dr Vanessa and Da Silva Filipe, Dr Ana and Gunson, Dr Rory and Ray, Professor Surajit and Divala, Dr Titus and Smollett, Dr Katherine and Wilkie, Dr Craig and MacLean, Dr Alasdair and McDonald, Dr Sarah and Allan, Mr Jay
Authors: Ho, A., Orton, R., Tayler, R., Asamaphan, P., Herder, V., Davis, C., Tong, L., Smollett, K., Manali, M., Allan, J., Rawlik, K., McDonald, S. E., Vink, E., Pollock, L., Gannon, L., Evans, C., McMenamin, J., Roy, K., Marsh, K., Divala, T., Holden, M. T.G., Lockhart, M., Yirrell, D., Currie, S., O'Leary, M., Henderson, D., Shepherd, S. J., Jackson, C., Gunson, R., MacLean, A., McInnes, N., Bradley-Stewart, A., Battle, R., Hollenbach, J., Henderson, P., Odam, M., Chikowore, P., Oosthuyzen, W., Chand, M., Shea Hamilton, M., Estrada-Rivadeneyra, D., Levin, M., Avramidis, N., Pairo-Castineira, E., Vitart, V., Wilkie, C., Palmarini, M., Ray, S., Robertson, D. L., da Silva Filipe, A., Willett, B. J., Breuer, J., Semple, M. G., Turner, D., Baillie, J. K., and Thomson, E. C.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
College of Medical Veterinary and Life Sciences > School of Life Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
College of Science and Engineering > School of Mathematics and Statistics > Statistics
Journal Name:Nature
Publisher:Nature Research
ISSN (Online):1476-4687
Published Online:30 March 2023
Copyright Holders:Copyright © 2023 The Authors
First Published:First published in Nature 617(7961): 555-563
Publisher Policy:Reproduced with the permission of the Publisher
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172630014Cross-Cutting Programme – Viral Genomics and Bioinformatics (Programme 9)David RobertsonMedical Research Council (MRC)MC_UU_12014/12III - Centre for Virus Research
310665ISARIC - Coronavirus Clinical Characterisation ConsortiumAntonia HoMedical Research Council (MRC)MC_PC_19059 - 9815274III - Centre for Virus Research
301049Host determinants of disease outcomes in arboviral infectionsMassimo PalmariniWellcome Trust (WELLCOTR)206369/Z/17/ZIII - Centre for Virus Research