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

被引：94

作者：

Ho, Antonia ^{[1
]}

Orton, Richard ^{[1
]}

Tayler, Rachel

Asamaphan, Patawee ^{[1
]}

Herder, Vanessa ^{[1
]}

Davis, Chris ^{[1
]}

Tong, Lily ^{[1
]}

Smollett, Katherine ^{[1
]}

Manali, Maria ^{[1
]}

Allan, Jay ^{[1
]}

Rawlik, Konrad ^{[3
]}

McDonald, Sarah E. ^{[1
]}

Vink, Elen ^{[1
]}

Pollock, Louisa ^{[1
,2
]}

Gannon, Louise ^{[4
]}

Evans, Clair ^{[5
]}

McMenamin, Jim ^{[6
]}

Roy, Kirsty ^{[6
]}

Marsh, Kimberly ^{[6
]}

Divala, Titus ^{[6
]}

Holden, Matthew T. G. ^{[6
]}

Lockhart, Michael ^{[6
]}

Yirrell, David ^{[6
]}

Currie, Sandra ^{[6
]}

O'Leary, Maureen ^{[6
]}

Henderson, David ^{[6
]}

Shepherd, Samantha J. ^{[7
]}

Jackson, Celia ^{[7
]}

Gunson, Rory ^{[7
]}

MacLean, Alasdair ^{[7
]}

McInnes, Neil ^{[7
]}

Bradley-Stewart, Amanda ^{[8
]}

Battle, Richard ^{[9
]}

Hollenbach, Jill A. ^{[10
,11
]}

Henderson, Paul ^{[12
]}

Odam, Miranda ^{[3
]}

Chikowore, Primrose ^{[3
]}

Oosthuyzen, Wilna ^{[3
]}

Chand, Meera ^{[13
]}

Hamilton, Melissa Shea ^{[14
]}

Estrada-Rivadeneyra, Diego ^{[14
]}

Levin, Michael ^{[14
]}

Avramidis, Nikos ^{[3
]}

Pairo-Castineira, Erola ^{[3
]}

Vitart, Veronique ^{[3
,15
]}

Wilkie, Craig ^{[16
]}

Palmarini, Massimo ^{[1
]}

Ray, Surajit ^{[16
]}

Robertson, David L. ^{[1
]}

Filipe, Ana da Silva ^{[1
]}

机构：

[1] Univ Glasgow, Med Res Council, Ctr Virus Res, Glasgow, Lanark, Scotland

[2] Royal Hosp Children, Dept Paediat, Glasgow, Lanark, Scotland

[3] Univ Edinburgh, Ctr Inflammat Res & Roslin Inst, Pandem Sci Hub, Edinburgh, Midlothian, Scotland

[4] NHS Tayside, Dept Paediat, Dundee, Scotland

[5] Queen Elizabeth Univ Hosp, Dept Pathol, Glasgow, Lanark, Scotland

[6] Publ Hlth Scotland, Glasgow, Lanark, Scotland

[7] West Scotland Specialist Virol Ctr, Glasgow, Lanark, Scotland

[8] Ninewells Hosp, Virol Lab, Dundee, Scotland

[9] Royal Edinburgh Infirm, Scottish Natl Blood Transfus Serv, Histocompatibil & Immunogenet H&I Lab, Edinburgh, Midlothian, Scotland

[10] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA

[11] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA

[12] Univ Edinburgh, Child Life & Hlth, Edinburgh, Midlothian, Scotland

[13] UK Hlth Secur Agcy, London, England

[14] Imperial Coll London, Dept Infect Dis, Sect Paediat Infect Dis, London, England

[15] Univ Edinburgh, Inst Genet & Canc, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland

[16] Univ Glasgow, Sch Math & Stat, Glasgow, Lanark, Scotland

[17] UCL, London, England

[18] Univ Liverpool, Pandem Inst, Liverpool, Merseyside, England

[19] London Sch Hyg & Trop Med, Dept Clin Res, London, England

来源：

NATURE | 2023年 / 617卷 / 7961期

基金：

英国科研创新办公室; 英国惠康基金; 英国生物技术与生命科学研究理事会; 英国医学研究理事会;

关键词：

REAL-TIME PCR; HEPATOCYTES; HEMOPHILIA; DIAGNOSIS;

D O I：

10.1038/s41586-023-05948-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

An outbreak of acute hepatitis of unknown aetiology in children was reported in Scotland(1) in April 2022 and has now been identified in 35 countries(2). Several recent studies have suggested an association with human adenovirus with this outbreak, a virus not commonly associated with hepatitis. Here we report a detailed case-control investigation and find an association between adeno-associated virus2 (AAV2) infection and host genetics in disease susceptibility. Using next-generation sequencing, PCR with reverse transcription, serology and in situ hybridization, we detected recent infection with AAV2 in plasma and liver samples in 26 out of 32 (81%) cases of hepatitis compared with 5 out of 74 (7%) of samples from unaffected individuals. Furthermore, AAV2 was detected within ballooned hepatocytes alongside a prominent Tcell infiltrate in liver biopsy samples. In keeping with a CD4(+) T-cell-mediated immune pathology, the human leukocyte antigen (HLA) classII HLA-DRB1*04:01 allele was identified in 25 out of 27 cases (93%) compared with a background frequency of 10 out of 64 (16%; P=5.49x10(-12)). In summary, we report an outbreak of acute paediatric hepatitis associated with AAV2 infection (most likely acquired as a co-infection with human adenovirus that is usually required as a 'helper virus' to support AAV2 replication) and disease susceptibility related to HLA classII status. A case-control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

引用

页码：555 / +

页数：25

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