Genetic Features Of Hepatitis E Virus In Cross-Species Infection And Effects Of Viral Persistent Infection On Host Cells

Hepatitis E virus(HEV)is a RNA virus which has been regarded as a zoonotic pathogen and carries out for infection via ‘fecal-oral' pathway.According to expanding host range of HEV infection,swine,termed as biological ‘mixture' for cross-species infection of HEV between human and other animals,plays an important role in HEV prevalence in human population.Moreover,HEV infection can lead to viral persistent infection.Due to a big scale of swine farms in China,either pig farm or free-range pigs has a potential to transmit HEV to raisers,and consumption of undercooked pork products has been regarded as an important transmission route to human.Base on the threats of cross-species of HEV infection and HEV persistent infection to human,we depended on some methods including serology,molecular biology,cellular biology and bioinformatics to investigate into genetic features for HEV derived from human or swine and interactions between virus and host during viral persistent infection.Firstly,serological prevalence of HEV infection in pig farms in 7 provinces,China has been carried out,and genetic information about HEV strain derived from pig farms in Gansu province has been obtained by molecular method.In these 7 provinces,a high serological prevalence is in pig farms,and the age and breeding purposes play important roles in the risk of HEV infection in pigs.Moreover,genetic information of HEV derived from Gansu province represents genotype 4e.Furthermore,bioinformatic analyses represent genetic diversities for open reading frames(ORFs)between swine HEV and human HEV at the aspect of synonymous codon usage patterns for genotype 1,genotype 3 and genotype 4,but genotype 1 HEV ORF1 owns genotype-specific synonymous codon usage patterns.As for genotype 3 and genotype 4 HEV,swine HEV shows more adaptation to human than that of human HEV.This result implies that HEV meeting with selection pressure from host shows adaptation to cellular environment of host.Depending on HEV persistent infection model and transcriptomics,it is found that HEV persistent infection alters biological processes including many metabolic pathways at aspect of gene transcription in order to make a trade-off with host cells.However,infected cells also stimulate gene transcription related to immune responses to response to HEV persistent infection.Here,we detected 14 genes related to antiviral responses and found that I,II and III types interferon(IFN)genes significantly up-regulate their transcription levels and ISG 15,ISG56 and MX1 genes significantly do that as well.At the same time,IL-6,CCL5 and CXCL 10 which all are involved in antiviral responses and inflammation significantly get up their transcriptional levels,particularly CXCL 10 gene.This result suggests that CXCL 10 plays an important role in HEV persistent infection,providing some new insights into clinical therapy for HEV persistent infection.In this study,these results expand our views for cross-species of HEV infection and HEV persistent infection in order to deeply understand evolutional dynamic of HEV and interaction between viral persistent infection and host cells.