Adeno-associated virus type 2 in US children with acute severe hepatitis.
Adeno-associated virus type 2 in US children with acute severe hepatitis.
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DOI：
10.1038/s41586-023-05949-1
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发表时间：
2023-05
期刊：
影响因子：
64.8
通讯作者：
Chiu, Charles Y
中科院分区：
文献类型：
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作者：
Servellita, Venice;Sotomayor Gonzalez, Alicia;Lamson, Daryl M;Foresythe, Abiodun;Huh, Hee Jae;Bazinet, Adam L;Bergman, Nicholas H;Bull, Robert L;Garcia, Karla Y;Goodrich, Jennifer S;Lovett, Sean P;Parker, Kisha;Radune, Diana;Hatada, April;Pan, Chao-Yang;Rizzo, Kyle;Bertumen, J Bradford;Morales, Christina;Oluniyi, Paul E;Nguyen, Jenny;Tan, Jessica;Stryke, Doug;Jaber, Rayah;Leslie, Matthew T;Lyons, Zin;Hedman, Hayden D;Parashar, Umesh;Sullivan, Maureen;Wroblewski, Kelly;Oberste, M Steven;Tate, Jacqueline E;Baker, Julia M;Sugerman, David;Potts, Caelin;Lu, Xiaoyan;Chhabra, Preeti;Ingram, L Amanda;Shiau, Henry;Britt, William;Gutierrez Sanchez, Luz Helena;Ciric, Caroline;Rostad, Christina A;Vinje, Jan;Kirking, Hannah L;Wadford, Debra A;Raborn, R Taylor;St George, Kirsten;Chiu, Charles Y
截至2022年8月，包括美国在内的35个国家报告了病因不明的儿童急性重型肝炎聚集性病例。先前的研究已经在欧洲和美国患者的血液中发现了人类腺病毒（HAdVs），尽管尚不清楚这种病毒是否具有致病性。在这里，我们使用PCR检测、基于病毒富集的测序和不可知的宏基因组测序分析了从2021年10月1日至2022年5月22日期间来自16例hadv阳性病例的样本，同时分析了113例对照。在14例患者的血液中，93%（14例中的13例）检测到腺相关病毒2型（AAV2）序列，而在113例对照中检测到4例（3.5%）（P < 0.001），在30例病因明确的肝炎患者中检测到0例（P < 0.001）。在对照组中，23例急性胃肠炎（无肝炎）患者中有9例（39.1%）血液中检出hav 41型，其中9例粪便hav检测阳性患者中有8例（39.1%），但这23例患者中只有3例（13.0%）同时感染AAV2型，而93%的病例（P < 0.001）。14例患者中有12例（85.7%）同时感染eb病毒、人疱疹病毒6型和/或肠道病毒A71型，其中疱疹病毒检出率高于对照组（P < 0.001）。我们的研究结果表明，疾病的严重程度与涉及AAV2和一种或多种辅助病毒的合并感染有关。一项使用PCR检测、基于病毒富集的测序和不可知性宏基因组测序的回顾性分析发现，腺相关病毒2型与不明原因的儿童肝炎之间存在关联。
As of August 2022, clusters of acute severe hepatitis of unknown aetiology in children have been reported from 35 countries, including the USA. Previous studies have found human adenoviruses (HAdVs) in the blood from patients in Europe and the USA, although it is unclear whether this virus is causative. Here we used PCR testing, viral enrichment-based sequencing and agnostic metagenomic sequencing to analyse samples from 16 HAdV-positive cases from 1 October 2021 to 22 May 2022, in parallel with 113 controls. In blood from 14 cases, adeno-associated virus type 2 (AAV2) sequences were detected in 93% (13 of 14), compared to 4 (3.5%) of 113 controls (P < 0.001) and to 0 of 30 patients with hepatitis of defined aetiology (P < 0.001). In controls, HAdV type 41 was detected in blood from 9 (39.1%) of the 23 patients with acute gastroenteritis (without hepatitis), including 8 of 9 patients with positive stool HAdV testing, but co-infection with AAV2 was observed in only 3 (13.0%) of these 23 patients versus 93% of cases (P < 0.001). Co-infections by Epstein–Barr virus, human herpesvirus 6 and/or enterovirus A71 were also detected in 12 (85.7%) of 14 cases, with higher herpesvirus detection in cases versus controls (P < 0.001). Our findings suggest that the severity of the disease is related to co-infections involving AAV2 and one or more helper viruses. A retrospective analysis using PCR testing, viral enrichment-based sequencing and agnostic metagenomic sequencing finds an association between adeno-associated virus type 2 and paediatric hepatitis of unknown cause.