Dataset Information

Genetic variability of human adenovirus type 7 circulating in mainland China.

ABSTRACT: Human adenovirus (HAdV-7) is a highly contagious pathogen that causes severe respiratory illnesses. However, the epidemic patterns and genetic variability of HAdV-7 circulating in mainland China have not been well elucidated. In this study, we used Chinese HAdV sentinel surveillance data obtained from 2012-2015 to investigate the clinical features of 122 HAdV-7-positive cases and performed amplification and sequence determination of three capsid genes (penton base, hexon, and fiber) from 69 isolated viruses covering from seven provinces of China. Additionally, we compared with data from representative sequences of 21 strains covering seven more provinces in China and 32 international HAdV-7 strains obtained from GenBank database to determine the phylogenetic, sequence variations, and molecular evolution of HAdV-7. The results indicated that HAdV-7 infection occurred throughout the year, and a high proportion of severe cases (27 cases, 22.1%) exhibited infantile pneumonia. Moreover, phylogenetic analysis showed that all HAdV-7 strains could be divided into two major evolutionary branches, including subtype 1 and subtype 2, and subtype 3 was also formed according to analysis of the penton base gene. Subtypes 1 and 2 co-circulated in China before 2008, and HAdV-7 strains currently circulating in China belonged to subtype 2, which was also the predominant strain circulating worldwide in recent years. Further sequence variation analysis indicated that three genes of HAdV-7 were relatively stable across time and geographic space, particularly for viruses within subtypes, which shared almost the same variation sites. Owing to continuous outbreaks caused by HAdV-7, resulting in increased illness severity and fatality rates in China, the establishment of a national HAdV surveillance system is urgently needed for the development of effective preventive and infection-control interventions for adenovirus respiratory infections in China.

SUBMITTER: Cai R

PROVIDER: S-EPMC7192419 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Genetic variability of human adenovirus type 7 circulating in mainland China.

Cai Ru R Mao Naiying N Dai Jingjing J Xiang Xingyu X Xu Jing J Ma Yingwei Y Li Zhong Z Han Guangyue G Yu Deshan D Yin Jie J Cui Aili A Zhang Yan Y Li Hong H Yu Pengbo P Guan Luyuan L Tian Yuling Y Sun Liwei L Li Yan Y Wei Yamei Y Zhu Zhen Z Xu Wenbo W

PloS one 20200430 4

Human adenovirus (HAdV-7) is a highly contagious pathogen that causes severe respiratory illnesses. However, the epidemic patterns and genetic variability of HAdV-7 circulating in mainland China have not been well elucidated. In this study, we used Chinese HAdV sentinel surveillance data obtained from 2012-2015 to investigate the clinical features of 122 HAdV-7-positive cases and performed amplification and sequence determination of three capsid genes (penton base, hexon, and fiber) from 69 isol ...[more]

PMID: 32352995

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Project description: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.

Project description:Type 31 of human adenovirus species A (HAdV-A31) is a significant pathogen primarily associated with diarrhoea in children but also with life-threatening disseminated disease in allogeneic haematopoietic stem cell transplant (HSCT) recipients. Nosocomial outbreaks of HAdV-A31 have been frequently described. However, the evolution of HAdV-A31 has not been studied in detail. The evolution of other HAdV types is driven either by intertypic recombination, where different types exchange genome regions, or by immune escape selection of neutralisation determinants. Complete genomic HAdV-A31 sequences from sixty diagnostic specimens of the past 18 years (2003-21) were generated, including fourteen specimens of a presumed outbreak on two HSCT wards. Additionally, twenty-three complete genomes from GenBank were added to our phylogenetic analysis as well as in silico generated and previously published restriction fragment polymorphism (RFLP) data. Phylogenetic analysis of eighty-three genomes indicated that HAdV-A31 evolved slowly with six lineages co-circulating. The two major lineages were lineage 1, which included the prototype from 1962 and nine recent isolates, and lineage 2, which split into four sublineages and included most isolates from 2003 to 2021. The average nucleotide identity within lineages was high (99.8 per cent) and identity between lineages was 98.7 and 99.2 per cent. RFLP data allowed the construction of a lower-resolution phylogeny with two additional putative lineages. Surprisingly, regions of higher diversity separating lineages were found in gene regions coding for non-structural and minor capsid proteins. Intertypic recombinations were not observed, but the phylogeny of lineage 3 was compatible with an interlineage recombination event in the fibre gene. Applying the phylogenetic analysis to the presumed nosocomial outbreak excluded two suspected transmission events and separated it into two different, simultaneous outbreaks caused by different sublineages of lineage 2. However, due to the high nucleotide identity within HAdV-A31 lineages, the proof of infection chains remains debatable. This in-depth study on the molecular phylogeny of HAdV-A31 highlights the high genetic stability of co-circulating HAdV-A31 lineages over almost six decades. It also supports the epidemiological hypothesis that HAdV-A31 circulates as an etiological agent of a childhood disease infecting immunologically naive patients without strong positive selection of immune escape variants and recombinants.

Dataset Information

Genetic variability of human adenovirus type 7 circulating in mainland China.

Publications

Genetic variability of human adenovirus type 7 circulating in mainland China.

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