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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Adeno-associated virus 2 infection in children with non-A–E hepatitis
Nature, Volume 617, No. 7961, Year 2023
Notification
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Description
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 countries2. 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 virus 2 (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 T cell infiltrate in liver biopsy samples. In keeping with a CD4+ T-cell-mediated immune pathology, the human leukocyte antigen (HLA) class II 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 = 5.49 × 10−12). 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 class II status. © 2023, The Author(s), under exclusive licence to Springer Nature Limited.
Authors & Co-Authors
Ho, Antonia Yw
United Kingdom, London
Medical Research Council
Orton, Richard J.
United Kingdom, London
Medical Research Council
Asamaphan, Patawee
United Kingdom, London
Medical Research Council
Davis, Christopher A.
United Kingdom, London
Medical Research Council
Tong, Lily
United Kingdom, London
Medical Research Council
Rawlik, Konrad C.
United Kingdom, Midlothian
University of Edinburgh, Roslin Institute
Pollock, Louisa
United Kingdom, London
Medical Research Council
United Kingdom, Glasgow
Royal Hospital for Children, Glasgow
Marsh, Kimberly Anne
United Kingdom, Edinburgh
Public Health Scotland
Divala, Titus Henry
United Kingdom, Edinburgh
Public Health Scotland
Holden, Matthew T.G.
United Kingdom, Edinburgh
Public Health Scotland
Yirrell, David L.
United Kingdom, Edinburgh
Public Health Scotland
Shepherd, Samantha J.
United Kingdom, Glasgow
West of Scotland Specialist Virology Centre
Gunson, Rory N.
United Kingdom, Glasgow
West of Scotland Specialist Virology Centre
Bradley-Stewart, Amanda J.
United Kingdom, Dundee
Ninewells Hospital
Hollenbach, Jill Allison
United States, San Francisco
University of California, San Francisco
Henderson, Paul M.
United Kingdom, Edinburgh
The University of Edinburgh
United Kingdom, Edinburgh
Nhs Lothian
Odam, Miranda
United Kingdom, Midlothian
University of Edinburgh, Roslin Institute
Chikowore, Primrose
United Kingdom, Midlothian
University of Edinburgh, Roslin Institute
Oosthuyzen, Wilna
United Kingdom, Midlothian
University of Edinburgh, Roslin Institute
Chand, Meera A.
United Kingdom, London
Uk Health Security Agency
Hamilton, Shea
United Kingdom, London
Imperial College London
Estrada-Rivadeneyra, Diego
United Kingdom, London
Imperial College London
Levin, Michael L.
United Kingdom, London
Imperial College London
Pairo-Castineira, Erola
United Kingdom, Midlothian
University of Edinburgh, Roslin Institute
Vitart, Véronique
United Kingdom, Midlothian
University of Edinburgh, Roslin Institute
United Kingdom, Edinburgh
The University of Edinburgh
Cunnington, Aubrey J.
United Kingdom, London
Imperial College London
Herberg, Jethro Adam
United Kingdom, London
Imperial College London
Kaforou, Myrsini
United Kingdom, London
Imperial College London
Bellos, Evangelos
United Kingdom, London
Imperial College London
Broderick, Claire
United Kingdom, London
Imperial College London
Channon-Wells, Samuel William
United Kingdom, London
Imperial College London
Cooray, Samantha
United Kingdom, London
Imperial College London
De, Tisham
United Kingdom, London
Imperial College London
D’Souza, Giselle
United Kingdom, London
Imperial College London
Elorrieta, Leire Estramiana
United Kingdom, London
Imperial College London
Galassini, Rachel
United Kingdom, London
Imperial College London
Habgood-Coote, Dominic
United Kingdom, London
Imperial College London
Jackson, Heather R.
United Kingdom, London
Imperial College London
Kavanagh, James
United Kingdom, London
Imperial College London
Marjaneh, Mahdi Moradi
United Kingdom, London
Imperial College London
Menikou, Stephanie
United Kingdom, London
Imperial College London
Nichols, Samuel J.
United Kingdom, London
Imperial College London
Nijman, Ruud Gerard
United Kingdom, London
Imperial College London
Patel, Harsita
United Kingdom, London
Imperial College London
Pennisi, Ivana
United Kingdom, Midlothian
University of Edinburgh, Roslin Institute
United Kingdom, London
Imperial College London
Powell, Oliver
United Kingdom, London
Imperial College London
Reid, Ruth
United Kingdom, London
Imperial College London
Shah, Priyen
United Kingdom, London
Imperial College London
Vito, Ortensia
United Kingdom, London
Imperial College London
Whittaker, Elizabeth A.
United Kingdom, London
Imperial College London
Wilson, Clare M.
United Kingdom, London
Imperial College London
Womersley, Rebecca S.
United Kingdom, London
Imperial College London
Abdulla, Amina F.
United Kingdom, London
St Mary's Hospital
Darnell, Sarah
United Kingdom, London
St Mary's Hospital
Mustafa, Sobia
United Kingdom, London
St Mary's Hospital
Georgiou, Pantelis
United Kingdom, London
Imperial College London
Moser, Nicolas
United Kingdom, London
Imperial College London
Tibby, Shane M.
United Kingdom, London
Guy's and st Thomas' Nhs Foundation Trust
United Kingdom, London
King's College London
Kenny, Julia M.
United Kingdom, London
Guy's and st Thomas' Nhs Foundation Trust
Wellman, Paul A.
United Kingdom, London
Guy's and st Thomas' Nhs Foundation Trust
Shankar-Hari, Manu
United Kingdom, London
King's College London
United Kingdom, London
Guy's and st Thomas' Nhs Foundation Trust
Fidler, Katy J.
United Kingdom, Worthing
University Hospitals Sussex Nhs Foundation Trust
Agranoff, Daniel D.
United Kingdom, Worthing
University Hospitals Sussex Nhs Foundation Trust
Richmond, Vivien
United Kingdom, Worthing
University Hospitals Sussex Nhs Foundation Trust
Faust, Saul N.
United Kingdom, Southampton
University of Southampton
Liebeschuetz, Susan
United Kingdom, London
Newham University Hospital
Riddell, Anna C.
United Kingdom, London
The Royal London Hospital
Peters, Mark John
United Kingdom, London
Great Ormond Street Hospital for Children Nhs Foundation Trust
United Kingdom, London
Ucl Great Ormond Street Institute of Child Health
Bamford, A. R.J.
United Kingdom, London
Great Ormond Street Hospital for Children Nhs Foundation Trust
United Kingdom, London
Ucl Great Ormond Street Institute of Child Health
O’Neill, Lauran
United Kingdom, London
Great Ormond Street Hospital for Children Nhs Foundation Trust
Pathan, Nazima
United Kingdom, Cambridge
Addenbrooke's Hospital
United Kingdom, Cambridge
University of Cambridge
White, Deborah K.
United Kingdom, Cambridge
Addenbrooke's Hospital
Heightman, Melissa J.
United Kingdom, London
University College London Hospitals Nhs Foundation Trust
Drysdale, Simon Bruce
United Kingdom, London
St George's Hospital
Moots, Robert John
United Kingdom, Liverpool
Aintree University Hospital
Deep, Akash
United Kingdom, London
King's College Hospital
Gormley, Stuart
United Kingdom, Sheffield
Sheffield Children's Hospital
Paulus, Stéphane C.
United Kingdom, Oxford
Oxford University Hospitals Nhs Foundation Trust
United Kingdom, Oxford
University of Oxford
Pollard, Andrew J.
United Kingdom, Oxford
Oxford University Hospitals Nhs Foundation Trust
United Kingdom, Oxford
University of Oxford
United Kingdom, Oxford
Nihr Oxford Biomedical Research Centre
Shrestha, Shrijana R.
Nepal, Kathmandu
Patan Academy of Health Sciences
Gurung, Meeru
Nepal, Kathmandu
Patan Academy of Health Sciences
Pokhrel, Bhishma R.
Nepal, Kathmandu
Patan Academy of Health Sciences
Bijukchhe, Sanjeev Man
Nepal, Kathmandu
Patan Academy of Health Sciences
Martinón-Torres, Federico
Spain, Santiago de Compostela
Hospital Clínico Universitario de Santiago
Spain, Santiago de Compostela
Universidad de Santiago de Compostela
González, Fernando Álvez
Spain, Santiago de Compostela
Hospital Clínico Universitario de Santiago
Spain, Santiago de Compostela
Universidad de Santiago de Compostela
Bello, Xabier
Spain, Santiago de Compostela
Hospital Clínico Universitario de Santiago
Spain, Santiago de Compostela
Universidad de Santiago de Compostela
Spain, Santiago de Compostela
Instituto de Investigación Sanitaria de Santiago de Compostela
Ben García, Mirian
Spain, Santiago de Compostela
Hospital Clínico Universitario de Santiago
Spain, Santiago de Compostela
Universidad de Santiago de Compostela
Carnota, Sandra
Spain, Santiago de Compostela
Hospital Clínico Universitario de Santiago
Spain, Santiago de Compostela
Universidad de Santiago de Compostela
Cebey-López, Miriam
Spain, Santiago de Compostela
Hospital Clínico Universitario de Santiago
Spain, Santiago de Compostela
Universidad de Santiago de Compostela
Currás-Tuala, María José
Spain, Santiago de Compostela
Hospital Clínico Universitario de Santiago
Spain, Santiago de Compostela
Universidad de Santiago de Compostela
Suárez, Carlos Durán
Spain, Santiago de Compostela
Hospital Clínico Universitario de Santiago
Spain, Santiago de Compostela
Universidad de Santiago de Compostela
Vicente, Luisa García
Spain, Santiago de Compostela
Hospital Clínico Universitario de Santiago
Spain, Santiago de Compostela
Universidad de Santiago de Compostela
Gõmez-Carballa, Alberto
Spain, Santiago de Compostela
Hospital Clínico Universitario de Santiago
Spain, Santiago de Compostela
Universidad de Santiago de Compostela
Rial, Jose Gómez
Spain, Santiago de Compostela
Hospital Clínico Universitario de Santiago
Spain, Santiago de Compostela
Universidad de Santiago de Compostela
Iglesias, Pilar Leboráns
Spain, Santiago de Compostela
Hospital Clínico Universitario de Santiago
Spain, Santiago de Compostela
Universidad de Santiago de Compostela
Martinón-Torres, Nazareth
Spain, Santiago de Compostela
Hospital Clínico Universitario de Santiago
Spain, Santiago de Compostela
Universidad de Santiago de Compostela
Sánchez, José María
Spain, Santiago de Compostela
Hospital Clínico Universitario de Santiago
Spain, Santiago de Compostela
Universidad de Santiago de Compostela
Pérez, Belén Mosquera
Spain, Santiago de Compostela
Hospital Clínico Universitario de Santiago
Spain, Santiago de Compostela
Universidad de Santiago de Compostela
Pardo-Seco, Jacobo
Spain, Santiago de Compostela
Hospital Clínico Universitario de Santiago
Spain, Santiago de Compostela
Universidad de Santiago de Compostela
Pischedda, Sara
Spain, Santiago de Compostela
Hospital Clínico Universitario de Santiago
Spain, Santiago de Compostela
Universidad de Santiago de Compostela
Calle, Irene Rivero
Spain, Santiago de Compostela
Hospital Clínico Universitario de Santiago
Spain, Santiago de Compostela
Universidad de Santiago de Compostela
Rodríguez-Tenreiro, Carmen
Spain, Santiago de Compostela
Hospital Clínico Universitario de Santiago
Spain, Santiago de Compostela
Universidad de Santiago de Compostela
Redondo Collazo, Lorenzo
Spain, Santiago de Compostela
Hospital Clínico Universitario de Santiago
Spain, Santiago de Compostela
Universidad de Santiago de Compostela
Fernández, Sonia Serén
Spain, Santiago de Compostela
Hospital Clínico Universitario de Santiago
Spain, Santiago de Compostela
Universidad de Santiago de Compostela
Carrol, Enitan D.
United Kingdom, Liverpool
University of Liverpool
United Kingdom, Liverpool
Alder Hey Children's Hospital
Khanijau, Aakash
United Kingdom, Liverpool
University of Liverpool
Romaine, Sam T.
United Kingdom, Liverpool
University of Liverpool
Tsolia, Maria N.
Greece, Athens
Aghia Sophia Children's Hospital
Eleftheriou, Irini
Greece, Athens
Aghia Sophia Children's Hospital
Spyridis, Nikos P.
Greece, Athens
Aghia Sophia Children's Hospital
Maritsi, Despoina N.
Greece, Athens
Aghia Sophia Children's Hospital
Emonts, Marieke
United Kingdom, Newcastle
Newcastle University
United Kingdom, Newcastle
The Newcastle Upon Tyne Hospitals Nhs Foundation Trust
Lim, Emma J.
United Kingdom, Newcastle
The Newcastle Upon Tyne Hospitals Nhs Foundation Trust
United Kingdom, Newcastle
Newcastle University
Isaacs, John D.
United Kingdom, Newcastle
Newcastle University
van der Velden, Fabian Johannes Stanislaus
United Kingdom, Newcastle
Newcastle University
United Kingdom, Newcastle
The Newcastle Upon Tyne Hospitals Nhs Foundation Trust
Rojo, Pablo
Spain, Madrid
Servicio Madrileño de Salud
Spain, Madrid
Universidad Complutense de Madrid
Epalza, Cristina
Spain, Madrid
Servicio Madrileño de Salud
Spain, Madrid
Instituto de Investigación Hospital 12 de Octubre
Kuijpers, Taco W.
Netherlands, Amsterdam
Emma Kinderziekenhuis
Netherlands, Amsterdam
Stichting Sanquin Bloedvoorziening
Van Furth, A. M.
Netherlands, Amsterdam
Emma Kinderziekenhuis
Pajkrt, Dasja
Netherlands, Amsterdam
Emma Kinderziekenhuis
van Hensbroek, Michael Boele
Netherlands, Amsterdam
Emma Kinderziekenhuis
Romani, Lorenza
Italy, Rome
Irccs Ospedale Pediatrico Bambino Gesù
de Luca, Maia
Italy, Rome
Irccs Ospedale Pediatrico Bambino Gesù
Chiurchiù, Sara
Italy, Rome
Irccs Ospedale Pediatrico Bambino Gesù
Vermont, Clementien L.
Netherlands, Rotterdam
Erasmus Mc
Moll, Henriëtte A.
Netherlands, Rotterdam
Erasmus Mc
Hagedoorn, Nienke N.
Netherlands, Rotterdam
Erasmus Mc
Dik, Willem Arnout
Netherlands, Rotterdam
Erasmus Mc
Zavadska, Dace
Latvia, Riga
Riga Stradins University
Latvia, Riga
Bērnu Klīniskā Universitātes Slimnīca
Rudzate, Aleksandra
Latvia, Riga
Riga Stradins University
Latvia, Riga
Bērnu Klīniskā Universitātes Slimnīca
Mommert-Tripon, Marine
Unknown Affiliation
Brengel-Pesce, Karen
Unknown Affiliation
Pokorn, Marko
Slovenia, Ljubljana
Univerzitetni Klinični Center Ljubljana
Slovenia, Ljubljana
Univerza V Ljubljani
Kolnik, Mojca
Slovenia, Ljubljana
Univerzitetni Klinični Center Ljubljana
Avĉin, Tadej
Slovenia, Ljubljana
Univerzitetni Klinični Center Ljubljana
Slovenia, Ljubljana
Univerza V Ljubljani
Vincek, Katarina
Slovenia, Ljubljana
Univerzitetni Klinični Center Ljubljana
van der Flier, Michiel
Netherlands, Utrecht
University Medical Center Utrecht
Netherlands, Utrecht
Princess Máxima Center for Pediatric Oncology
Wösten-van Asperen, Roelie M.
Netherlands, Utrecht
University Medical Center Utrecht
Vastert, Bas J.
Netherlands, Utrecht
University Medical Center Utrecht
Bont, Louis J.
Netherlands, Utrecht
University Medical Center Utrecht
Netherlands, Utrecht
Princess Máxima Center for Pediatric Oncology
Beudeker, Coco R.
Netherlands, Utrecht
University Medical Center Utrecht
Netherlands, Utrecht
Princess Máxima Center for Pediatric Oncology
Agyeman, Philipp Kwame Abayie
Switzerland, Bern
University of Bern
Switzerland, Zurich
Kinderspital Zürich
Schlapbach, Luregn J.
Switzerland, Zurich
Kinderspital Zürich
Australia, Brisbane
The University of Queensland
Pósfay-Barbe, Klara Maria
Switzerland, Geneva
Hôpitaux Universitaires de Genève
Heininger, Ulrich
Switzerland, Basel
Universitat Basel
Kahlert, Christian R.
Switzerland, St Gallen
Children's Hospital of Eastern Switzerland
Riedel, Thomas
Unknown Affiliation
Berger, Christoph Tobias
Switzerland, Zurich
Kinderspital Zürich
Fink, Colin G.
United Kingdom, Coventry
University of Warwick
Voice, Marie
United Kingdom, Coventry
University of Warwick
Calvo-Bado, Leo A.
United Kingdom, Coventry
University of Warwick
Steele, Michael
United Kingdom, Coventry
University of Warwick
Zenz, Werner M.
Austria, Graz
Medizinische Universität Graz
Binder, Alexander
Austria, Graz
Medizinische Universität Graz
Kohlmaier, Benno
Austria, Graz
Medizinische Universität Graz
Kohlfürst, Daniela S.
Austria, Graz
Medizinische Universität Graz
Schweintzger, Nina Alexandra
Austria, Graz
Medizinische Universität Graz
Sagmeister, Manfred G.
Austria, Graz
Medizinische Universität Graz
Benesch, Martin
Austria, Graz
Medizinische Universität Graz
Eber, Ernst
Austria, Graz
Medizinische Universität Graz
van Keulen, Daniëlle
Unknown Affiliation
von Both, Ulrich
Germany, Munich
Ludwig-maximilians-universität München
Germany, Munich
Partner Site Munich
Kolberg, Laura
Germany, Munich
Ludwig-maximilians-universität München
Danhauser, Katharina
Germany, Munich
Ludwig-maximilians-universität München
Hoffmann, Florian
Germany, Munich
Ludwig-maximilians-universität München
Griese, Matthias
Germany, Munich
Ludwig-maximilians-universität München
Feuchtinger, Tobias
Germany, Munich
Ludwig-maximilians-universität München
Lurz, Eberhard
Germany, Munich
Ludwig-maximilians-universität München
Maier, Esther Maria
Germany, Munich
Ludwig-maximilians-universität München
Reiter, Karl
Germany, Munich
Ludwig-maximilians-universität München
Yeung, Shunmay M.
United Kingdom, London
London School of Hygiene & Tropical Medicine
United Kingdom, London
Imperial College London
Bath, David
United Kingdom, London
London School of Hygiene & Tropical Medicine
Fitchett, Elizabeth J.A.
United Kingdom, London
London School of Hygiene & Tropical Medicine
Cresswell, Fiona Valarie
United Kingdom, London
London School of Hygiene & Tropical Medicine
Usuf, Effua Abigail
Gambia, Banjul
Medical Research Council Laboratories Gambia
Ndure, Ebrahim
Gambia, Banjul
Medical Research Council Laboratories Gambia
Bojang, Kalifa A.
Gambia, Banjul
Medical Research Council Laboratories Gambia
Sarr, Isatou
Gambia, Banjul
Medical Research Council Laboratories Gambia
Semple, Malcolm Gracie
United Kingdom, Liverpool
University of Liverpool
United Kingdom, Liverpool
Alder Hey Children's Hospital
Carson, Gail Lindsay
United Kingdom, Oxford
University of Oxford
Openshaw, Peter J.M.
United Kingdom, London
Imperial College London
United Kingdom, London
Imperial College Healthcare Nhs Trust
Dunning, Jake W.
United Kingdom, London
Imperial College London
United Kingdom, London
Public Health England
Merson, Laura
United Kingdom, Oxford
University of Oxford
Russell, Clark Donald
United Kingdom, Edinburgh
University of Edinburgh, College of Medicine and Veterinary Medicine
Zambon, Maria C.
United Kingdom, London
Public Health England
Tedder, Richard S.
United Kingdom, London
Public Health England
United Kingdom, Bristol
Nhs Blood and Transplant
United Kingdom, London
Imperial College London
Khoo, Saye H.
United Kingdom, Liverpool
University of Liverpool
Turtle, Lance C.W.
United Kingdom, Liverpool
University of Liverpool
United Kingdom, Liverpool
Royal Liverpool University Hospital
Solomon, Tom
United Kingdom, Liverpool
University of Liverpool
United Kingdom, Liverpool
The Walton Centre Nhs Foundation Trust
Ijaz, Samreen
United Kingdom, London
Public Health England
Fletcher, Tom E.
United Kingdom, Liverpool
Liverpool School of Tropical Medicine
Thomson, Emma C.
United Kingdom, London
Medical Research Council
United Kingdom, London
London School of Hygiene & Tropical Medicine
Price, Nicholas Martin
United Kingdom, London
King's College London
United Kingdom, London
Guy's and st Thomas' Nhs Foundation Trust
Breuer, Judith M.
United Kingdom, London
University College London
de Silva, Thushan I.
United Kingdom, Sheffield
The University of Sheffield
Donohue, Chloe
United Kingdom, Liverpool
University of Liverpool
Hardwick, Hayley E.
United Kingdom, Liverpool
University of Liverpool
Clohisey, Sara M.R.
United Kingdom, Midlothian
University of Edinburgh, Roslin Institute
Law, Andrew S.
United Kingdom, Midlothian
University of Edinburgh, Roslin Institute
Fawkes, Angie
Unknown Affiliation
Gilchrist, Tammy
Unknown Affiliation
Murphy, Lee D.
Unknown Affiliation
Wrobel, Nicola
Unknown Affiliation
Brotherton, Helen
United Kingdom, Wishaw
University Hospital Wishaw
Fullerton, Duncan G.
United Kingdom, Crewe
Leighton Hospital
Grammatikopoulos, Tassos
United Kingdom, London
King's College Hospital
United Kingdom, London
King's College London
McGill, Fiona
United Kingdom, Leeds
Leeds Teaching Hospitals Nhs Trust
Collins, Emma L.
United Kingdom, Hereford
Wye Valley Nhs Trust
Palmarini, Massimo
United Kingdom, London
Medical Research Council
Robertson, David L.
United Kingdom, London
Medical Research Council
Willett, Brian J.
United Kingdom, London
Medical Research Council
Semple, Malcolm Gracie
United Kingdom, Liverpool
University of Liverpool
Baillie, John Kenneth
United Kingdom, Midlothian
University of Edinburgh, Roslin Institute
United Kingdom, Edinburgh
The University of Edinburgh
Statistics
Citations: 31
Authors: 213
Affiliations: 128
Identifiers
Doi:
10.1038/s41586-023-05948-2
ISSN:
00280836
Research Areas
Genetics And Genomics
Infectious Diseases
Maternal And Child Health