Genetic diversity and phylogenetic characteristics of human adenovirus strains 40/41 circulating in Yantai, China, during 2017-2019

Abstract

This study systematically characterizes the genetic diversity, phylogenetic relationships, recombination events, and structural variations of human adenovirus serotypes 40 and 41 (HAdV-F40/41) circulating in Shandong Province, China, between 2017 and 2019. A total of 2,221 stool samples were collected from patients presenting with acute gastroenteritis in Yantai. Enteric adenoviruses were identifiedusing real-time quantitative PCR targeting the hexon gene. Whole-genome sequencing was performed via nanopore and Illumina platforms, enabling high-resolution phylogenetic reconstruction with IQ-TREE and the identificationof recombination events using RDP5 and SimPlot. Evolutionary dynamics were inferred through Bayesian molecular clock analysis, while AlphaFold3-based structural modeling was used to assess the impact of genomic changes on the hexon protein. HAdV-F40/41 was detected in 94 samples (4.23%) with year-to-year variability in prevalence. Phylogenetic analysis revealed the co-circulation of multiple genetically distinct lineages, while recombination mapping identifiedkey breakpoints, notably within the hexon and pVII genes. The estimated recent divergence of dominant lineages suggests ongoing adaptive evolution. Structural modeling of the recombinant strain SD376 identified14 amino acid substitutions and three deletions relative to the reference strain OP378826.1, without substantial conformational alteration. These findingsprovide critical insights into the genomic plasticity and evolutionary potential of HAdV-F40/41, underscoring the importance of continuous genomic surveillance. The observed mutations and recombination patterns may facilitate immune escape and viral persistence, reinforcing the urgent need for improved monitoring strategies and the development of targeted vaccines.