Genomic Characteristics Of Human Adenovirus Type 4 Isolated From Four Provinces In China

Objective:The genetic characteristic and molecular evolution of human adenovirus type 4(HAdV-4)were preliminary studied in order to provide important basic scientific data for surveillance,diagnosis and control of HAdV-4 related diseases in mainland China,as well as vaccine research and development.Method:Virus isolation was conducted among the HAdV-4 positive clinical specimens from febrile respiratory syndrome surveillance cases during 2013-2015.And then three target genes including Penton base,Hexon,and Fiber and whole genome sequence(WGS)were amplified and determined for HAdV-4 strains.Meanwhile,the above gene sequences of HAdV-4 circulated in China and abroad were also downloaded from GenBank database for the gene database construction,and with which,the study on the genetic characteristic and molecular evolution were performed by using relevant bioinformatics software.Results:(1)Total 6 HAdV-4 strains were obtained among febrile respiratory syndrome surveillance cases from Shaanxi(2 strains),Yunnan(2 strains),Jilin(1 strains),and Shandong(1 strains)during 2013-2015 covering northeast,east,northwest and southwest of China;(2)The result of phylogenetic analysis indicated that HAdV-4 strains worldwide could be divided into two lineages including HAdV-4p and HAdV-4a,and HAdV-4 strains that has been prevalent in mainland China since 2008 belong to HAdV-4a,which was consistent with the global dominant strains;(3)Both HAdV-4p and HAdV-4a strains showed significant conservation and stability of the sequences within the genome across time and space,and nucleotide and amino acid mutations are closely related to different lineages;(4)The WGSs of 6 HAdV-4 strains in this study were 35965-35969bp in length,56.26-56.29%in guanine(G)+cytosine(C)content,and there were 47 Open Reading Frames(ORFs).(5)Bayesian MCMC tree of HAdV-4 trains based on WGS also could be divided into two lineages(HAdV-4p and HAdV-4a),which was consistent with result the phylogenetic tree based on three target genes.The estimated evolution rates of HAdV-4 based on WGS was 8.24×10-6 substitution/site/year,and the most recent common ancestor of HAdV-4a and HAdV-4p could be traced back to 1915 and 1900,respectively,and HAdV-4a might be introduced into China around 1984.(6)Three regions including ITR、E3 RID-alpha protein and E3 CRI-beta protein belonged to highly variable regions of HAdV-4,and nucleotide and amino acid mutations are closely related to different lineages.While the HAdV-4 strains circulated in China were highly conserved in these region.Conclusions:This study is the first to elucidate the genetic characteristics,genetic polymorphism and dynamic variation of HAdV-4 strains from acute respiratory infection cases in China.It further accumulates and enriches the database of HAdV virology surveillance in China,and provides important scientific and technological support for the prevention and control of HAdV-4 and vaccine development in China.Figure[seventeen]table[nine]reference[sixty-six]...