Genomic Characterization of Human Adenovirus Type 21 Strains - 7 PLADs, China, 2023-2024

Recent sentinel surveillance has revealed a rising prevalence of human adenovirus type 21 (HAdV-21) among HAdV infections in China. This study aimed to elucidate the molecular features of currently circulating HAdV-21 strains in China.

Whole-genome sequencing (WGS) was performed on 23 HAdV-21 strains isolated from acute respiratory infection cases, 56.5% involving lower respiratory tract infections, across 7 Chinese sentinel surveillance provincial-level administrative divisions (PLADs) (2023-2024). These sequences, along with 50 previously reported HAdV-21 genomes from 6 countries (1956-2019), were integrated into a WGS dataset for comprehensive phylogenetic, genetic variation, and recombination analyses.

WGS categorized the HAdV-21 strains into 3 subtypes: HAdV-21a, HAdV-21b, and historical HAdV-21p (isolated in the 1950s). HAdV-21a (1956-2024, involving 5 of the 6 countries) and HAdV-21b (2005-2024, involving 3 of the 6 countries) exhibited extensive spatiotemporal distributions. Recent Chinese strains (2023-2024) belonged to HAdV-21a and HAdV-21b (HAdV-21a/b), showing extremely high genetic homology with Chinese 2019 strains (genetic distance: 0.00007) and global strains (distance: <0.00040). Phylogenetic analysis confirmed that HAdV-21a/b shared a common ancestor and maintained a highly conserved genome despite decades of circulation. Sequence variation analysis identified shared and subtype-specific mutations in these two subtypes. Recombination pattern analysis further revealed that HAdV-21a/b acquired an HAdV-3-derived fragment in the E4 region (breakpoint: nt32,843).

Recombinant HAdV-21a/b subtypes have co-circulated in China in recent years with remarkable genetic conservation. Enhanced surveillance is essential to quantify associated disease burden and guide targeted prevention and control strategies.