Remarkable increase in the detection and molecular characterization of adenovirus F41 in children with acute gastroenteritis in Japan, 2017-2023.

Human adenovirus (HAdV) is one of the causative viruses of acute gastroenteritis (AGE) in children worldwide. Species F is known to be enteric adenovirus (genotypes 40 and 41) detected in stool samples. In Japan, we conducted an epidemiological study and molecular characterization of HAdV before and after the COVID-19 pandemic from 2017 to 2023. Among 821 patients, HAdV was detected in 118 AGE cases (14.4%). During a period of 6 years, the HAdV detection rates for each year were relatively low at 3.7% and 0%, in 2017-2018, and 2020-2021, respectively. However, the detection rate increased to remarkably high rates, ranging from 13.3% to 27.3% in the other 4-year periods. Of these HAdV-positive strains, 83.1% were F41 genotypes and 16.9% were other genotypes (A31, B3, C1, C2/C6, and C5). Phylogenetic analyses of the nucleotide and deduced amino acid sequences of the full-length hexon gene demonstrated that HAdV-F41 strains were comprised of three clades, and each clade was distributed across the study period from 2017 to 2023. Analysis of deduced amino acid sequences of the hexon gene of the representative HAdV-F41 strains from each clade revealed numerous amino acid substitutions across hypervariable regions (HVRs) from HVR-1 to HVR-7, two insertions in HVR-1 and HVR-7, and two deletions in HVR-1 and HVR-2 of the hexon gene compared to those of the prototype strain, particularly, those of clade 3 HAdV-F41 strains. The findings suggested that the HAdV-F41 of each clade was stable, conserved, and co-circulated for over two decades in Japan.