Genomic Characterization Analysis Of Human Adenovirus Species C Strains Isolated In Five Provinces Of China

Human adenovirus(HAdV),which belong to the genus Mastadenovirus in the family Adenoviridae,is a nonenveloped,double-stranded linear DNA virus with an icosahedral capsid.The size of the HAdV genome is about 36Kb,and Hexon,Penton base,and Fiber are the three major capsid proteins of HAdV.As of April 2021,HAdV can be divided into seven species(A-G)and 104 genotypes.So far,seven genotypes of human adenovirus species C(HAdV-C)including HAdV-C1,HAdV-C2,HAdV-C5,HAdV-C6,HAdV-C57?HAdV-89 and HAdV-C104 have been reported.HAdV-C is the main pathogen causing respiratory infections among children,and more than 80%of the population has been infected during their childhood.HAdV-C can escape the major histocompatibility complex type I immune response and establish a persistent infection characterized by the intermittent detoxification of the immunocompetent host,so that the virus can survive in the human body for a long time.The unique long-term persistent infection characteristics of HAdV-C can create more opportunities for the co-infection and genetic recombination between different types of HAdV within species C.Currently,although only three novel types of recombinant HAdV-C(HAdV-C57,HAdV-89 and HAdV-C 104)have been officially named,several studies have confirmed that there are many different genetic recombination patterns for HAdV-C circulated in China.According to the typing results based on the three target genes(Penton base,Hexon,and Fiber)in the previous study,ten HAdV-C strains were randomly selected from five provinces in mainland of China(Shanxi,Hunan,Yunnan,Gansu,and Hebei)for the determination and analysis of the whole genome sequences(WGS).After viral amplification and identification with real-time PCR method,WGS was obtained by segmented amplification and sequence splicing.Meanwhile,WGS of the seven HAdV-C prototype strains and the representative international HAdV-C strains were downloaded from the GenBank and the database for sequence analysis were constructed.Bioinformatics software was used to analyze the genome characteristics,phylogeny and gene recombination of ten HAdV-C strains.The results of this study showed that all 10 strains belonged to recombinant viruses between different HAdV types within species C.Take strain Yunnan2014-5733 as an example,it was constructed with the HAdV-104 as the backbone and exchanged with the HAdV-2 gene fragment in the hexon gene;for stain Shanxi2002-126,it might take HAdV-6 as the backbone,and recombined with HAdV-57 in the Fiber gene.Further study indicated that HAdV-5 was involoved in the genetic recombination events for most HAdV-C strains(six strains),which might be related to its high prevalence in the population.Comparison analysis with international HAdV-C strains showed that frequent and relatively complex recombination events occurred among HAdV-C strains,and most of the strains had relatively unique geneic recombination patterns.It is worth noting that four strains(Shanxi 2003-141,Hunan2014-S024,Hebei2011-6845 and Yunan2014-2932)might cause pathogenic changes after geneic recombination.For example,stain Hunan2014-S024 isolated from a child with severe acute respiratory infection had the highest homology with the strain MK041244-CHN-2006 from the stool specimens of healthy children in 2006,while penton base gene was replaced by gene fragment from stain MK041246-CHN-2012 from a child with pneumonia in Hunan Province in 2012.It is speculated that strain Hunan2014-S024 might have changed its pathogenicity after genetic recombination,therefore causing serious clinical manifestations.In addition,two of the 10 strains were detected with no evidence of genetic recombination.For example,strain Gansu2015-1546 and the Yunnan2014-4318 derived from respiratory infection cases,showed highly homologous with the virus strains circulated in Gansu province in the same year and the German strain in 2017,respectively,which indicated that recombinant viruses of the same source continued to circulate in the same province or different regions,presumably that it may due to the relatively short prevalence of these virus strains(one month and three years,respectively)and the low probability of recombination events.In summary,this study carried out the genetic characteristics and recombination evolution analysis of HAdV-C strains isolated from five provinces of China(Gansu,Hunan,Yunnan,Shanxi and Hebei)based on the whole genome sequence.The results of this sutdy further enrich the background data of the molecular characteristic of HAdV-C strains circulated in mainland of China,and also provide significant basic scientific data for the prevention and control of HAdV-C-related infectious diseases.