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

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.