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

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Ho, Antonia, Orton, Richard, Tayler, Rachel, Asamaphan, Patawee, Herder, Vanessa, Davis, Chris, Tong, Lily, Smollett, Katherine, Manali, Maria, Allan, Jay et al (show 48 more authors) , Rawlik, Konrad, McDonald, Sarah E, Vink, Elen, Pollock, Louisa, Gannon, Louise, Evans, Clair, McMenamin, Jim, Roy, Kirsty, Marsh, Kimberly, Divala, Titus, Holden, Matthew TG, Lockhart, Michael, Yirrell, David, Currie, Sandra, O'Leary, Maureen, Henderson, David, Shepherd, Samantha J, Jackson, Celia, Gunson, Rory, MacLean, Alasdair, McInnes, Neil, Bradley-Stewart, Amanda, Battle, Richard, Hollenbach, Jill, Henderson, Paul, Odam, Miranda, Chikowore, Primrose, Oosthuyzen, Wilna, Chand, Meera, Hamilton, Melissa Shea, Estrada-Rivadeneyra, Diego, Levin, Michael, Avramidis, Nikos, Pairo-Castineira, Erola, Vitart, Veronique, Wilkie, Craig, DIAMONDS consortium, , ISARIC4C investigators, , Palmarini, Massimo, Ray, Surajit, Robertson, David L, da Silva Filipe, Ana, Willett, Brian J, Breuer, Judith, Semple, Malcolm G, Turner, David, Baillie, J Kenneth and Thomson, Emma C (2023) Adeno-associated virus 2 infection in children with non-A-E hepatitis. Nature, 617 (7961). pp. 555-563.

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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.

Item Type:	Article
Uncontrolled Keywords:	DIAMONDS consortium, ISARIC4C investigators
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User:	Symplectic Admin
Date Deposited:	28 Apr 2023 08:32
Last Modified:	30 Sep 2023 01:30
DOI:	10.1038/s41586-023-05948-2
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3169939