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

Ho, A. et al. (2022) Adeno-associated virus 2 infection in children with non-A-E hepatitis. medRxiv, (doi: 10.1101/2022.07.19.22277425) (Submitted)

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Abstract

An outbreak of acute hepatitis of unknown aetiology in children was first reported in Scotland in April 2022.1 Cases aged <16 years have since been identified in 35 countries.2 Here we report a detailed investigation of 9 early cases and 58 control subjects. Using next-generation sequencing and real-time PCR, adeno-associated virus 2 (AAV2), was detected in the plasma of 9/9 and liver of 4/4 patients but in 0/13 sera/plasma of age-matched healthy controls, 0/12 children with adenovirus (HAdV) infection and normal liver function and 0/33 children admitted to hospital with hepatitis of other aetiology. AAV2 typically requires a coinfecting ‘helper’ virus to replicate, usually HAdV or a herpesvirus. HAdV (species C and F) and human herpesvirus 6B (HHV6B) were detected in 6/9 and 3/9 affected cases, including 3/4 and 2/4 liver biopsies, respectively. The class II HLA-DRB1*04:01 allele was identified in 8/9 cases (89%), compared with a background frequency of 15.6% in Scottish blood donors, suggestive of increased susceptibility in affected cases. Acute non-A-E paediatric hepatitis is associated with the presence of AAV2 infection, which could represent a primary pathogen or a useful biomarker of recent HAdV or HHV6B infection. Population and mechanistic studies are required to explore these findings further.

Item Type:Articles
Status:Submitted
Refereed:No
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 Tong, Dr Lily and Davis, Dr Chris and Evans, Clair and Pollock, Dr Louisa and Orton, Dr Richard and Da Silva Filipe, Dr Ana and Gunson, Dr Rory and Divala, Dr Titus and Smollett, Dr Katherine and MacLean, Dr Alasdair and McDonald, Dr Sarah
Authors: Ho, A., Orton, R., Tayler, R., Asamaphan, P., Tong, L., Smollett, K., Davis, C., Manali, M., McDonald, S. E., Pollock, L., Evans, C., McMenamin, J., Roy, K., Marsh, K., Divala, T., Holden, M., Lockhart, M., Yirrell, D., Currie, S., Shepherd, S. J., Jackson, C., Gunson, R., MacLean, A., McInnes, N., Battle, R., Hollenbach, J., Henderson, P., Chand, M., Shea Hamilton, M., Estrada-Rivadeneyra, D., Levin, M., Robertson, D. L., Filipe, A., Willett, B., 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 Life Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:medRxiv
Copyright Holders:Copyright © 2022 The Authors
Publisher Policy:Reproduced under a Creative Commons License
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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