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Human Adenovirus Subtype 21a Isolates From Children With Severe Lower Respiratory Illness in China
Wenkuan Liu1, Li Zhang1, Yong Cai1
1State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Health Guangzhou Medical University, Guangzhou, China.
Insights
Human adenovirus type 21 (HAdV-21) caused severe respiratory illness in children in China. This study characterized two HAdV-21a strains, revealing genetic differences that impact antibody response, crucial for vaccine development.
Area of Science:
- Virology
- Infectious Diseases
- Epidemiology
Background:
- Human adenovirus type 21 (HAdV-21) is a significant cause of acute respiratory infection (ARI) but has been underreported and poorly characterized.
- HAdV was the third most common pathogen detected in hospitalized pediatric patients with ARI in Guangzhou, China, in 2019.
Purpose of the Study:
- To report and characterize HAdV-21 infections in pediatric patients in China.
- To analyze the genetic diversity and antigenic properties of HAdV-21 strains.
- To assess the implications for HAdV-21 epidemiology, pathogenicity, and vaccine development.
Main Methods:
- Sequencing and phylogenetic analysis of two HAdV-21a isolates from severe ARI cases.
- Comparison of viral replication and plaque formation with the prototype strain.
- Immunization of mice with different HAdV-21 branches and assessment of neutralizing antibody titers.
Main Results:
- Two HAdV-21a strains were identified in children with severe lower respiratory illness, closely related to a strain found in Bengbu, China.
- Phylogenetic analysis revealed two main branches of HAdV-21, with significant variations in hexon protein's highly variable regions between branches.
- Mice immunized with one HAdV-21 branch exhibited reduced neutralizing antibody titers against the other branch.
Conclusions:
- This study provides the first report of HAdV-21a infections in children in China, detailing two isolates associated with severe respiratory illness.
- The genetic and antigenic differences identified between HAdV-21 branches are critical for understanding HAdV-21 epidemiology and pathogenicity.
- Findings highlight the need for considering antigenic diversity in the development of effective HAdV-21 vaccines and antiviral strategies.
Abstract:
Human adenovirus type 21 (HAdV-21) is an important pathogen associated with acute respiratory infection (ARI), but it was rarely reported and characterized so far. In this study, 151 of 1,704 (8.9%) pediatric patients (≤14 years old) hospitalized with ARI in Guangzhou, China in 2019 were positive for HAdV which was the third most frequently detected pathogen. Two HAdV-21-positive patients presented with severe lower respiratory illness and had similar initial symptoms at onset of illness. Then two HAdV-21 strains were isolated and characterized. The two HAdV-21 strains were sequenced and classified as subtype 21a with genomes closely related to strain BB/201903 found in Bengbu, China in March 2019. Phylogenetic analysis for whole genome and major antigen proteins of global HAdV-21 strains showed that HAdV-21 could be classified into two branches, branch 1 including genotype 21p, branch 2 including all other strains dividing into genotype 21a and 21b. There was no significant difference in the plaque size, or the replication curves between the two HAdV-21a strains and the prototype strain HAdV-21p AV-1645. However, there were five highly variable regions (HVR1, HVR3, HVR4, HVR5, and HVR7) in the hexon protein that varied between two branches. Mice immunized with one branch strain showed 2-4-fold lower neutralizing antibody titers against another branch strain. In summary, this study firstly reported two HAdV-21a infections of children in China, characterized two isolates of HAdV-21a associated with severe lower respiratory illness; our results could be important for understanding the HAdV-21 epidemiology and pathogenic, and for developing HAdV-21 vaccine and drug.
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