Jinjin Wang, Ling Jing, Yali Duan, Junhong Ai, Yun Zhu, Ran Wang, Xiangpeng Chen, Gen Lu, Yun Sun, Changchong Li, Rong Jin, Yunxiao Shang, Yixiao Bao, Shuhua An, Yunlian Zhou, Limin Ning, Baoping Xu, Yuhai Bi and Zhengde Xie. Genetic analysis of human adenovirus type 108 circulating in China during 2014-2024[J]. Virologica Sinica, 2025, 40(5): 694-709. doi: 10.1016/j.virs.2025.09.002
Citation: Jinjin Wang, Ling Jing, Yali Duan, Junhong Ai, Yun Zhu, Ran Wang, Xiangpeng Chen, Gen Lu, Yun Sun, Changchong Li, Rong Jin, Yunxiao Shang, Yixiao Bao, Shuhua An, Yunlian Zhou, Limin Ning, Baoping Xu, Yuhai Bi, Zhengde Xie. Genetic analysis of human adenovirus type 108 circulating in China during 2014-2024 .VIROLOGICA SINICA, 2025, 40(5) : 694-709.  http://dx.doi.org/10.1016/j.virs.2025.09.002

2014-2024年我国流行的人腺病毒108型的基因分析

  • 通讯作者: 谢正德, xiezhengde@bch.com.cn
  • 收稿日期: 2025-04-17
    录用日期: 2025-09-11
  • 人腺病毒(Human adenovirus,HAdV)108型已在包括我国在内的多个国家被鉴定出来,并与儿童严重急性呼吸道感染(Acute respiratory infection,ARI)有关,并且有死亡病例报道。然而,目前对HAdV-108型的研究较少。本研究旨在调查HAdV-108型腺病毒感染在我国ARI儿童中的临床和基因特征。2014-2024年,在我国南部和北部10家医院共收集到因ARI住院患儿的呼吸道样本6720份,其中505例为腺病毒阳性。对全基因组和三个主要衣壳蛋白基因序列进行扩增测序并进行生物信息学分析,结果显示分离获得的317份HAdV阳性样本中21份(6.62%)被鉴定为HAdV-108,位于第三位,仅次于HAdV-114和HAdV-7型。收集HAdV-108阳性患儿的临床信息进行临床特征分析发现,患儿主要表现为咳嗽和发热。7名患儿出现胃肠道症状,2名无基础疾病的患儿被诊断为重症肺炎。全基因组系统进化分析表明,国内外的主要流行分支有很大的不同。本研究获得的1株毒株独立形成了1个分支。三种主要衣壳蛋白中六邻体(hexon)蛋白进化速率最快,一致性最低,氨基酸变异最大,而纤突(fiber)蛋白进化速率最慢,一致性最高,氨基酸最保守和稳定。与收集时间最早的HAdV-108毒株相比,本研究获得的毒株和2023年分离自我国的毒株在五邻体(penton base)蛋白的RGD loop区存在3个新的氨基酸缺失,蛋白同源建模发现可能存在结构差异。重组分析鉴定出5种不同的重组模式。体外实验表明,HAdV-108具有与HAdV-C种其他型别(包括亲本株HAdV-1和-2)相同的增殖能力。总而言之,HAdV-108在我国持续流行,感染后可导致严重的ARIs并伴随胃肠道表现。分支3是我国的主要流行分支。HAdV-108表现出显着的型内遗传变异,重组事件随机且多样。

Genetic analysis of human adenovirus type 108 circulating in China during 2014-2024

  • Corresponding author: Zhengde Xie, xiezhengde@bch.com.cn
  • Received Date: 17 April 2025
    Accepted Date: 11 September 2025
  • Human adenovirus type 108 (HAdV-108) has been detected in multiple countries, including China, and is associated with severe acute respiratory infection (ARI) in children, with reported fatalities. However, studies on HAdV-108 remain limited. This study aimed to investigate the clinical and genetic characteristics of HAdV-108 in ARI children in China. From 2014 to 2024, 6720 respiratory samples were collected from hospitalized children with ARI at ten hospitals across northern and southern China, of which 505 (7.51%) tested positive for HAdV. The whole-genome and three major capsid protein genes were amplified and sequenced for bioinformatics analysis, which revealed that among 317 HAdV-isolated samples, 21 (6.62%) were identified as HAdV-108, ranking third after HAdV-114 and HAdV-7. Clinical analysis of HAdV-108-positive cases showed that the main manifestations were cough and fever. Seven children had gastrointestinal symptoms, and two children without underlying diseases were diagnosed with severe pneumonia. Phylogenetic analysis of whole-genome sequences revealed distinct predominant epidemic branches between domestic and international strains, with one strain obtained in this study forming an independent branch. Hexon protein exhibited the fastest evolution rate, lowest identity, and greatest amino acid variability, while fiber protein displayed the slowest evolution rate, highest identity, and greatest conservation and stability. Compared with the earliest reported HAdV-108 strain, three amino acid deletions were identified in the RGD loop region of penton base protein, resulting in potential structural change. Recombination analysis identified five distinct recombination patterns. In vitro experiments demonstrated that HAdV-108 had proliferation capacity comparable to other species C adenoviruses. In summary, HAdV-108 has persistently circulated in China, causing severe ARIs and concurrent gastrointestinal manifestations. Cluster3 was the predominant epidemic branch in China. HAdV-108 exhibited significant intra-type genetic variation, with random and diverse recombination events.

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    Genetic analysis of human adenovirus type 108 circulating in China during 2014-2024

      Corresponding author: Zhengde Xie, xiezhengde@bch.com.cn
    • a. Beijing Key Laboratory of Core Technologies for the Prevention and Treatment of Emerging Infectious Diseases in Children, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, Research Unit of Critical Infection in Children, Chinese Academy of Medical Sciences, 2019RU016, Laboratory of Infection and Virology, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China;
    • b. Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 102629, China;
    • c. Department of Respiratory, GuangZhou Women and Children's Medical Center, GuangZhou, 510623, China;
    • d. Department of General Pediatrics, Yinchuan Women and Children Healthcare Hospital, Yinchuan, 750002, China;
    • e. Department of Respiratory, The 2nd Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China;
    • f. Department of Respiratory, Guiyang Maternal and Child Health Hospital, Guiyang, 550003, China;
    • g. Department of Pediatric Respiratory, Shengjing Hospital of China Medical University, Shenyang, 110004, China;
    • h. Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China;
    • i. Children's Hospital of Hebei Province, Shijiazhuang, 050031, China;
    • j. The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, China;
    • k. Children's Hospital of Changchun, Changchun, 130061, China;
    • l. National Clinical Research Center for Respiratory Diseases, Department of Respiratory Medicine, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China;
    • m. College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, 030801, China;
    • n. CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Center for Influenza Research and Early-warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences (CAS), Beijing, 100101, China;
    • o. University of Chinese Academy of Sciences, Beijing, 100049, China

    Abstract: Human adenovirus type 108 (HAdV-108) has been detected in multiple countries, including China, and is associated with severe acute respiratory infection (ARI) in children, with reported fatalities. However, studies on HAdV-108 remain limited. This study aimed to investigate the clinical and genetic characteristics of HAdV-108 in ARI children in China. From 2014 to 2024, 6720 respiratory samples were collected from hospitalized children with ARI at ten hospitals across northern and southern China, of which 505 (7.51%) tested positive for HAdV. The whole-genome and three major capsid protein genes were amplified and sequenced for bioinformatics analysis, which revealed that among 317 HAdV-isolated samples, 21 (6.62%) were identified as HAdV-108, ranking third after HAdV-114 and HAdV-7. Clinical analysis of HAdV-108-positive cases showed that the main manifestations were cough and fever. Seven children had gastrointestinal symptoms, and two children without underlying diseases were diagnosed with severe pneumonia. Phylogenetic analysis of whole-genome sequences revealed distinct predominant epidemic branches between domestic and international strains, with one strain obtained in this study forming an independent branch. Hexon protein exhibited the fastest evolution rate, lowest identity, and greatest amino acid variability, while fiber protein displayed the slowest evolution rate, highest identity, and greatest conservation and stability. Compared with the earliest reported HAdV-108 strain, three amino acid deletions were identified in the RGD loop region of penton base protein, resulting in potential structural change. Recombination analysis identified five distinct recombination patterns. In vitro experiments demonstrated that HAdV-108 had proliferation capacity comparable to other species C adenoviruses. In summary, HAdV-108 has persistently circulated in China, causing severe ARIs and concurrent gastrointestinal manifestations. Cluster3 was the predominant epidemic branch in China. HAdV-108 exhibited significant intra-type genetic variation, with random and diverse recombination events.

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