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Genetic analysis of human adenovirus type 108 circulating in China during 2014-2024
Jinjin Wang1, Ling Jing2, Yali Duan1
1Beijing 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.
Insights
Human adenovirus type 108 (HAdV-108) persistently circulates in China, causing severe acute respiratory infections (ARIs) and gastrointestinal symptoms in children. This study highlights its genetic diversity and distinct epidemic branches within China.
Area of Science:
- Virology
- Molecular Biology
- Public Health
Background:
- Human adenovirus type 108 (HAdV-108) is associated with severe acute respiratory infections (ARIs) in children globally.
- Limited studies exist on HAdV-108, particularly its clinical and genetic characteristics in China.
Purpose of the Study:
- To investigate the clinical manifestations and genetic features of HAdV-108 in children with ARI in China.
- To analyze the evolutionary dynamics and recombination patterns of HAdV-108.
Main Methods:
- Collection and testing of 6720 respiratory samples from children with ARI across China (2014-2024).
- Whole-genome and major capsid protein gene sequencing of HAdV isolates.
- Bioinformatic and phylogenetic analyses to determine genetic characteristics, evolution, and recombination.
Main Results:
- HAdV-108 was detected in 6.62% of HAdV-positive samples (21/317), ranking third in prevalence.
- Clinical manifestations included cough, fever, and gastrointestinal symptoms; severe pneumonia was observed in two children.
- Phylogenetic analysis revealed distinct domestic epidemic branches, with one novel strain forming an independent branch. Hexon protein showed high variability, while fiber protein was conserved. Three amino acid deletions were noted in the penton base RGD loop.
- Five recombination patterns were identified, and HAdV-108 showed proliferation capacity similar to other species C adenoviruses.
Conclusions:
- HAdV-108 is a persistent pathogen in China, causing severe ARIs and gastrointestinal issues in children.
- Cluster3 represents the predominant epidemic branch of HAdV-108 in China.
- Significant intra-type genetic variation and diverse recombination events characterize HAdV-108 evolution.
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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