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.
Highlights
Human adenoviruses (HAdVs) belonging to the Mastadenovirus genus of the Adenoviridae family (Knipe and Howley, 2013) are double-stranded non-enveloped DNA viruses, which have been grouped into seven species (HAdV-A to G), with 104 genotypes1
All the strains circulating in China from 2004 to 2020 including 54 isolates obtained in this study as well as parts of strains circulating in the United States, Japan, and South Korea constituted cluster 3 (Figure 1)
Compared with the prototype strain GB, an amino acid (AA) substitution (D327N) was observed at the Arg-Gly-Asp (RGD) loop in all strains circulating in China, and an AA substitution (T159I) was found at hypervariable region 1 (HVR1) in 54 isolates obtained in this study
Summary
Human adenoviruses (HAdVs) belonging to the Mastadenovirus genus of the Adenoviridae family (Knipe and Howley, 2013) are double-stranded non-enveloped DNA viruses, which have been grouped into seven species (HAdV-A to G), with 104 genotypes. HAdVs play a significant role in pediatric respiratory tract infections, especially in severe pneumonia, accounting for 3.5–11% of childhood community-acquired pneumonias (CAP) (Jain et al, 2015; Liu et al, 2015; Wang et al, 2015). HAdV infection can be severe, or even fatal, both in immunocompetent (Zarraga et al, 1992) and immunocompromised patients (Yu et al, 2016). HAdV-3, first isolated from a patient with acute respiratory infection (ARI) in the winter of 1952–1953, is one of the most prevalent serotypes responsible for respiratory infection diseases in children and adults worldwide (Lynch and Kajon, 2016). A number of studies have demonstrated that HAdV3 may lead to severe pneumonias in immunocompetent children (Rebelo-de-Andrade et al, 2010) and adults (Barker et al, 2003). Monitoring the prevalence of HAdV-3 in China and analyzing the genetic stability and amino acid (AA) variation of the HAdV-3 genome, especially in the hypervariable regions 1–7 (loops 1 and 2) of the hexon gene, are of great importance to develop vaccines and drugs against HAdV-3
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
