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Published on: January 28, 2016
Molecular Characteristics of Human Adenovirus Type 3 Circulating in Parts of China During 2014-2018
Yali Duan1, Baoping Xu1, Changchong Li2
1Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, 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, China.
Abstract:
Human adenoviruses (HAdVs) are important pathogens causing respiratory infections; 3.5-11% of childhood community-acquired pneumonia is associated with HAdV infection. Human adenovirus type 3 (HAdV-3), leading to severe morbidity and mortality, is one of the most prevalent genotype among adenoviruses responsible for acute respiratory infections (ARIs) in children in China. To identify the genetic variation of HAdV-3 in children with ARIs in China, a molecular epidemiological study was conducted. A total of 54 HAdV-3 isolated strains were obtained from children with ARIs in Beijing, Wenzhou, Shanghai, Shijiazhuang, Hangzhou, Guangzhou, and Changchun from 2014 to 2018. Thirty-two strains of which were selected for whole-genome sequencing, while the hexon, penton base, and fiber genes were sequenced for remaining strains. Bioinformatics analysis was performed on the obtained sequences. The phylogenetic analyses based on whole-genome sequences, major capsid protein genes (hexon, penton base, and fiber), and early genes (E1, E2, E3, and E4) showed that the HAdV-3 strains obtained in this study always clustered together with the reference strains from Chinese mainland, while the HAdV-3 prototype strain formed a cluster independently. Compared with the prototype strain, all strains possessed nine amino acid (AA) substitutions at neutralization antigenic epitopes of hexon. The homology models of the hexon protein of the HAdV-3 prototype and strain BJ20160214 showed that there was no evident structural change at the AA mutation sites. Two AA substitutions were found at the Arg-Gly-Asp (RGD) loop and hypervariable region 1 (HVR1) region of the penton base. A distinct AA insertion (20P) in the highly conserved PPPSY motif of the penton base that had never been reported before was observed. Recombination analysis indicated that partial regions of protein IIIa precursor, penton base, and protein VII precursor genes among all HAdV-3 strains in this study were from HAdV-7. This study showed that the genomes of the HAdV-3 strains in China were highly homologous. Some AA mutations were found at antigenic sites; however, the significance needs further study. Our data demonstrated the molecular characteristics of HAdV-3 circulating in China and was highly beneficial for further epidemiological exploration and the development of vaccines and drugs against HAdV-3.
Insights
Genetic analysis of Human Adenovirus type 3 (HAdV-3) in China reveals high genomic homology among circulating strains. Key mutations were identified in capsid proteins, with evidence of recombination with HAdV-7, informing future vaccine and drug development.
Area of Science:
- Virology
- Molecular Epidemiology
- Genetics
Background:
- Human adenoviruses (HAdVs) are significant causes of respiratory infections, particularly in children.
- Human Adenovirus type 3 (HAdV-3) is a prevalent genotype in China, associated with severe acute respiratory infections (ARIs).
Purpose of the Study:
- To investigate the genetic variations and molecular characteristics of HAdV-3 strains circulating in China.
- To understand the evolutionary patterns and potential for recombination in HAdV-3.
Main Methods:
- Molecular epidemiological study involving isolation of 54 HAdV-3 strains from children with ARIs across China (2014-2018).
- Whole-genome sequencing of 32 strains and sequencing of key genes (hexon, penton base, fiber) for the remaining strains.
- Bioinformatics and phylogenetic analyses, including homology modeling and recombination analysis.
Main Results:
- Phylogenetic analysis showed HAdV-3 strains clustered together, distinct from the prototype strain.
- Nine amino acid substitutions were identified in hexon neutralization epitopes, with no significant structural changes.
- Penton base gene revealed two amino acid substitutions and a novel insertion (20P) in the PPPSY motif.
- Recombination analysis indicated gene fragment exchange between HAdV-3 and HAdV-7.
Conclusions:
- HAdV-3 genomes in China exhibit high homology, with identified mutations in antigenic sites requiring further investigation.
- The study elucidates the molecular characteristics of circulating HAdV-3 strains in China.
- Findings provide valuable data for future epidemiological studies and the development of HAdV-3 targeted vaccines and therapeutics.
