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

Ho, Antonia; Orton, Richard; Asamaphan, Patawee; Herder, Vanessa; Davis, Chris; Tong, L.; Smollett, Katherine; Manali, Maria; Allan, Jay; Rawlik, Konrad; McDonald, Sarah E.; Vink, Elen; Evans, Clair; McMenamin, Jim; Roy, Kirsty; Marsh, Kimberly; Divala, Titus; Holden, Matthew T. G.; 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 A.; Henderson, Paul; Odam, Miranda; Chikowore, Primrose; Oosthuyzen, Wilna; Hamilton, Melissa Shea; Estrada-Rivadeneyra, Diego; Levin, Michael; Avramidis, Nikos; Pairo-Castineira, Erola; Vitart, Véronique; Wilkie, Craig; Cunnington, Aubrey J.; Herberg, Jethro; Kaforou, Myrsini; Wright, Victoria; Bellos, Evangelos; Broderick, Claire; Channon‐Wells, Samuel; Cooray, Samantha; De, Tisham; D’Souza, Giselle; Elorrieta, Leire Estramiana; Galassini, Rachel; Habgood-Coote, Dominic; Hamilton, Shea; Jackson, Heather; Kavanagh, James; Marjaneh, Mahdi Moradi; Menikou, Stephanie; Nichols, Samuel; Nijman, Ruud; Patel, Harsita; Powell, Oliver; Reid, Ruth; Shah, Priyen; Vito, Ortensia; Whittaker, Elizabeth; Wilson, Clare; Womersley, Rebecca; Abdulla, Amina; Darnell, Sarah; Mustafa, Sobia; Georgiou, Pantelis; Manzano, Jesus-Rodriguez; Moser, Nicolas; Pennisi, Ivana; Carter, Michael; Tibby, Shane M.; Cohen, Jonathan D.; Davis, Francesca; Kenny, Julia; Wellman, Paul J.; White, Marie; Fish, Matthew; Jennings, A.R.; Shankar-Hari, Manu; Fidler, Katy; Agranoff, Dan; Richmond, Vivien; Seal, Mathew; Faust, Saul N; Owen, Dan; Ensom, Ruth; McKay, Sarah; Mondo, Diana; Shaji, Mariya; Schranz, Rachel; Rughnani, Prita; Anpananthar, Amutha; Liebeschuetz, Susan; Riddell, Anna; Khalid, Nosheen; Malcolm, Ivone Lancoma; Simagan, Teresa; Peters, Mark; Bamford, Alasdair; O’Neill, Lauran; Pathan, Nazima; Daubney, Esther; White, Deborah L.; Heightman, Melissa; Eisen, Sarah; Segal, Terry; Wellings, Lucy; Drysdale, Simon B.; Branch, Nicole; Hamzah, Lisa; Jarman, Heather; Nyirenda, Maggie; Capozzi, Lisa; Gardiner, Emma; Moots, Robert J.; Nasher, Magda; Hanson, Anita; Linforth, Michelle; O’Riordan, Sean; Ellis, Donna; Deep, Akash; Caro, Iván; Shackley, Fiona; Bellini, Arianna; Gormley, Stuart; Neshat, Samira; Scholefield, Barnaby J.; Robbins, Ceri; Winmill, Helen; Paulus, Stéphane; Anthony, Mark; Hopton, Sarah; Miller, Danielle; Oliver, Zoe; Beer, Sally; Ward, Bryony; Shrestha, Shrijana; Pollard, Andrew J.; Gurung, Meeru; Amatya, Puja; Pokhrel, Bhishma; Kingdomchhe, Sanjeev Man BijUnited; Lubinda, Tim; Kelly, Sarah; O’Reilly, Peter; Martinón‐Torres, Federico; Salas, Antonio; González, Fernando Álvez; Bello, Xabier; García, Mirian Ben; Carnota, Sandra; Cebey-López, Miriam; Currás-Tuala, María José; Suárez, Carlos Durán; Vicente, Luisa García; Gómez-Carballa, Alberto; Rial, Jose Gómez; Iglesias, Pilar Leboráns; Martinón-Torres, Nazareth; Sánchez, José María Martinón; Pérez, Belén Mosquera; Pardo-Seco, Jacobo; Rodríguez, Lidia Piñeiro; Pischedda, Sara; Vázquez, Sara Rey; Rivero‐Calle, Irene; Rodrı́guez-Tenreiro, Carmen; Redondo-Collazo, Lorenzo; Ora, Miguel Sadiki; Fernández, Sonia Serén; Trasorras, Cristina Serén; Iglesias, Marisol Vilas; Carrol, Enitan D.; Cocklin, Elizabeth; Khanijau, Aakash; Lenihan, Rebecca; Lewis-Burke, Nadia; Newall, Karen; Romaine, Sam; Τσολιά, Μαρία; Eleftheriou, Irini; Spyridis, Νikos; Tambouratzi, Maria; Maritsi, Despoina; Marmarinos, Antonios; Xagorari, Marietta; Panagiota, Lourida; Aggelos, Pefanis; Karolina, Akinosoglou; Charalambos, Gogos; Markos, Maragos; Voulgarelis, Michalis; Ioanna, Stergiou; Emonts, Marieke; Lim, Emma; Isaacs, John T.; Bell, Kathryn; Crulley, Stephen; Fabián, Daniel; Thomson, Evelyn; Wallia, Diane; Miller, Caroline; Bell, Ashley; Velden, Fabian van der; Shenton, Geoff; Price, Ashley B.; Treloar, Owen; Thomas, Daisy; Murcia, Pablo R; Epalza, Cristina; Villaverde, Serena; Márquez, Sonia; Gijón, Manuel; Machín, Fátima; Cabello, Laura; Hernández, Irene; Gutiérrez, L.; Manzanares, Ángela; Kuijpers, T. W. Taco; Kuip, M. Martijn van de; Furth, A. M. Marceline van; Berg, J. M. Merlijn van den; Biesbroek, Giske; Verkuil, Floris; Zee, Carlijn C. W. van der; Pajkrt, Dasja; Hensbroek, Michaël Boele van; Schonenberg, D.; Gruppen, Mariken; Nagelkerke, Sietse Q.; Jansen, Machiel H.; Goetschalckx, Ines; Romani, Lorenza; Luca, Maia De; Chiurchiù, Sara; Giuseppe, Martina Di; Vermont, Clementien; Moll, Henriëtte A.; Borensztajn, Dorine; Hagedoorn, Nienke N.; Tan, Chantal; Zachariasse, Joany M; students, Medical; Dik, W.; Shen, Ching-Fen Kitty; Zavadska, Dace; Laivacuma, Sniedze; Rudzate, Aleksandra; Stoldere, Diana; Bārzdiņa, Arta; Barzdina, Elza; Madelāne, Monta; Grāvele, Dagne; Svile, Dace; Basmaci, Romain; Lachaume, Noémie; Bories, Pauline; Tkhayat, Raja Ben; Chériaux, Laura; Davoust, Juraté; Ong, Kim-Thanh; Cotillon, Marie; Groc, Thibault de; Lê, Sébastien; Vergnault, Nathalie; See, Hélène; Cohen, Laure; Tugny, Alice de; Danékova, Névéna; Mommert-Tripon, Marine; Brengel‐Pesce, Karen; Pokorn, Marko; Kolnik, Mojca; Avčin, Tadej; Avramoska, Tanja; Bahovec, Natalija; Bogovič, Petra; Kitanovski, Lidija; Nahtigal, Mirijam; Papst, Lea; Srovin, Tina Plankar; Strle, Franc; Srpčič, Anja; Vincek, Katarina; Flier, Michiel van der; Tissing, Wim J. E.; Asperen, Roelie M. Wösten–van; Vastert, Sebastiaan J.; Vijlbrief, Daniel C.; Bont, Louis; Wolfs, Tom F. W.; Beudeker, Coco R.; Usman, Mariama; Schlüchter, Stefanie; Wyss, Verena; Schöbi, Nina; Zimmermann, Elisa; Meier, Marion; Weber, Kathrin; Agyeman, Philipp; Schlapbach, Luregn J.; Giannoni, Éric; Stocker, Martin; Posfay‐Barbe, Klara M.; Heininger, Ulrich; Bernhard-Stirnemann, Sara; Niederer-Loher, Anita; Kahlert, Christian; Natalucci, Giancarlo; Relly, Christa; Riedel, Thomas; Aebi, Christoph; Berger, Christoph; Fink, Prof Colin; Voice, Marie; Calvo-Bado, Leo A.; Steele, Michael; Holden, Jennifer; Evans, B. J. K.; Stevens, Jake; Matthews, Peter; Billing, Kyle; Zenz, Werner; Binder, Alexander; Kohlmaier, Benno; Kohlfürst, Daniela S.; Schweintzger, Nina A.; Zurl, Christoph; Hösele, Susanne; Leitner, Manuel; Pölz, Lena; Rusu, Alexandra; Rajic, Glorija; Stoiser, Bianca; Strempfl, Martina; Sagmeister, Manfred G.; Bauchinger, Sebastian; Benesch, Martin; Ceolotto, Astrid; Eber, Ernst; Gallistl, Siegfried; Haidl, Harald; Hauer, Almuthe; Hude, Christa; Kapper, Andreas; Keldorfer, Markus; Löffler, Sabine; Niedrist, Tobias; Pilch, Heidemarie; Pfleger, Andreas; Pfurtscheller, Klaus; Rödl, Siegfried; Skrabl-Baumgartner, Andrea; Strenger, Volker; Wallner, Elmar; Tempel, Dennie; Keulen, Daniëlle van; Strijbosch, Annelieke M.; Tauchert, Maike K.; Both, Ulrich von; Kolberg, Laura; Schmied, Patricia; Alba-Alejandre, I; Danhauser, Katharina; Haas, Nikolaus A.; Hoffmann, Florian; Griese, Matthias; Feuchtinger, Tobias; Juranek, Sabrina; Kappler, Matthias; Lurz, Eberhard; Maier, Esther M.; Reiter, Karl; Schoen, Carola; Schroepf, Sebastian; Yeung, Shunmay; Dewez, Manuel; Bath, David; Fitchett, Elizabeth; Cresswell, Fiona V; Semple, Malcolm G; Carson, Gail; Openshaw, Peter; Dunning, Jake; Merson, Laura; Russell, Clark D; Dorward, David A.; Zambon, Maria; Chand, Meera; Tedder, Richard S.; Khoo, Saye; Turtle, Lance; Solomon, Tom; Ijaz, Samreen; Fletcher, Tom; Thomson, Emma C.; Price, Nicholas C.; Breuer, Judith; Silva, Thushan I. de; Donohue, Chloe; Hardwick, Hayley; Obosi, Lauren; Clohisey, Sara; Law, Andy; Norris, Lucy; Tait, Sarah; Wham, Murray; Clark, Richard E.; Coutts, Audrey; Donnelly, Lorna; Fawkes, Angie; Gilchrist, Tammy; Hafezi, Katarzyna; MacGillivray, Louise; Maclean, Alan; McCafferty, Sarah; Morrice, Kirstie; Murphy, Lee; Wrobel, Nicola; Shaw, Victoria; Ahmed, Katie A.; Armstrong, J. A.; Lett, Lauren; Henderson, Paul; Pollock, Louisa; Kishore, Shyla; Brotherton, Helen; Armstrong, Lawrence E.; Mitra, Andrew; Dall, Anna; Böhmová, Kristýna; Gannon, Louise; Agwuh, Ken; Chukkambotla, Srikanth; DuRand, Ingrid; Fullerton, Duncan; Gar, Sanjeev; Graham, C. D.; Grammatikopoulos, Tassos; Hartshorn, Stuart; Hodgson, Luke; Jennings, Paul; Koshy, George; Leiner, Tamás; Limb, James; Little, Jeff; Logan, Sheena; Matovu, Enock; McGill, Fiona; Morris, Craig F.; Morrice, John A.; Price, David; Reschreiter, Henrik; Reynolds, Tim; Whittaker, Paul A.; Jordan, Thomas H.; Tayler, Rachel; Irving, Clare; Jack, Katherine; Ramsay, Maxine; Millar, Margaret; Milligan, Barry; Hickey, Naomi; Connon, Maggie; Ward, Catriona; Beveridge, Laura; MacFarlane, Susan; Leitch, Karen; Bell, Claire; Finlayson, Lauren; Dawson, Joy; Candlish, Janie; McGenily, Laura; Roome, Tara; Diaba, Cynthia; Player, Jasmine; Powell, Natassia; Howman, Ruth; Burling, Sara; Floyd, Sharon; Farmer, Sarah; Ferguson, Susie; Hope, Susan; Rubick, Lucy; Swingler, Rachel; Collins, Emma; Spencer, Collette; Jones, Amaryl; Wilson, Barbara A.; Armstrong, Diane; Birt, Mark; Dickinson, Holly J.; Harper, R.; Martin, Darran; Roff, Amy; Mills, Sarah; Palmarini, Massimo; Ray, Surajit; Robertson, David L.; Filipe, Ana da Silva; Willett, Brian J.; Breuer, Judith; Semple, Malcolm G; Turner, David M.; Baillie, J Kenneth; Thomson, Emma C.

doi:10.1038/s41586-023-05948-2

Cited by 81 publications

(85 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the first study, researchers looked at 32 children who presented to hospital in Scotland with acute severe hepatitis of unknown aetiology from 14 March to 20 August 2022. They found recent infection with AAV2 in the plasma and liver samples of 26 of the 32 (81%) hepatitis cases, which compared with five of 74 (7%) in the control group 4…”

Section: Study Findingsmentioning

confidence: 97%

Unexplained hepatitis in children may be linked to adeno associated virus 2, studies find

Mahase¹

2023

BMJ

View full text Add to dashboard Cite

Section: Study Findingsmentioning

confidence: 97%

Unexplained hepatitis in children may be linked to adeno associated virus 2, studies find

Mahase¹

2023

BMJ

View full text Add to dashboard Cite

“…Emerging evidence indicates that intracellular ssDNA accumulates due to pathogen infection ( 6–8 ), Trex1 mutation ( 9 ), replication stress ( 10 ), chromosome instability ( 11 ), dysregulation of retrotransposon ( 12 ), R-loop accumulation ( 13 ), and gene therapy ( 14 ). Although the dsDNA-specific sensors cGAS ( 15, 16 ) and IFI16 ( 17 ) have been reported to mediate cytosolic ssDNA-induced type I interferon responses, they actually recognize double-stranded complementary stretches of ssDNA, rather than single-stranded structure ( 16, 18, 19 ).…”

Section: Main Textmentioning

confidence: 99%

“…Altogether, these in vivo results suggest that intracellular accumulation of stimulatory ssDNA can induce inflammation and hepatic necrosis and cause hepatitis in a SLFN9-dependent manner. Given the resemblance of these phenotypes to the AAV-induced severe hepatotoxicity observed during gene therapy and infection ( 6, 7, 37 ), SLFN11 may play a critical role in mediating AAV-induced immune responses in human.…”

Section: Main Textmentioning

confidence: 99%

Schlafen-11 and -9 are innate immune sensors for intracellular single-stranded DNA

Zhang,

Hu,

et al. 2024

Preprint

View full text Add to dashboard Cite

Nucleic acids are major structures detected by the innate immune system. Although intracellular single-stranded DNA (ssDNA) is accumulated during pathogen infection or pathogenesis, it remains unclear whether and how intracellular ssDNA stimulates the immune system. We report that intracellular ssDNA triggers cytokine expression and cell death in a CGT motif-dependent manner. Through a genome-wide CRISPR‒Cas9 screen, we identified Schlafen-11 (SLFN11), which is essential for the response to endogenous and pathogen ssDNA. SLFN11 directly binds ssDNA containing CGT motifs and translocates to the cytoplasm upon ssDNA recognition. The mice deficient in SLFN9, the homologue of SLFN11, were resistant to CGT ssDNA-induced inflammation, acute hepatitis and septic shock. This study establishes CGT ssDNA and SLFN11/9 as a novel type of immunostimulatory nucleic acids and pattern recognition receptors, respectively.

show abstract

“…57 Metagenomic analysis of liver tissue and blood also identified adeno-associated virus 2 in some children. 65,66 Adeno-associated virus is defective single-stranded DNA viruse that can only replicate in the presence of a helper virus. 59 The hypothesis of immunological predisposition/ genetic susceptibility in those affected was based on the identification of specific HLA class II allele, DRB1*04:01 in cases reported from the United Kingdom.…”

Section: Acute Severe Hepatitis Of Unknown Etiologymentioning

confidence: 99%

Viral Hepatitis Necessitating Liver Transplantation in Children

Valamparampil

Kelly

2023

Transplantation

View full text Add to dashboard Cite

Viral hepatitis accounts for a significant global disease burden and mortality, both in children and adults. There are significant differences in the viral etiology, epidemiology, and complications in children worldwide. Children of all ages may have devastating complications with a significant risk of mortality and long-term morbidity because of viral hepatitis. Liver transplantation is the only curative option for pediatric patients with end-stage liver disease, hepatocellular carcinoma, or acute liver failure because of viral hepatitis. The introduction of universal vaccination for hepatitis B across the world and hepatitis A in some countries had led to significant changes in the incidence of disease and the need for liver transplantation for the complications of viral hepatitis in children. The development of effective treatment with directly acting antiviral agents for hepatitis C has already transformed outcomes in adults and children and reduced the need for liver transplantation. Although newer therapy for hepatitis B is being evaluated in adults, current therapy for children is not curative, indicating the need for lifelong therapy and potential necessity for liver transplantation. The recent epidemic of acute hepatitis in children across the world has highlighted the importance of understanding the etiology of unusual causes for acute liver failure and the urgent need for liver transplantation.

show abstract

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

Cited by 81 publications

References 37 publications

Unexplained hepatitis in children may be linked to adeno associated virus 2, studies find

Unexplained hepatitis in children may be linked to adeno associated virus 2, studies find

Schlafen-11 and -9 are innate immune sensors for intracellular single-stranded DNA

Viral Hepatitis Necessitating Liver Transplantation in Children

Contact Info

Product

Resources

About