The Function Of MicroRNAs On Virus And Host

MicroRNA(miRNA)regulation was widely considered as a mechanism to control gene expression of animals and plants.Yet,it has been shown to interact with viruses to repress virus gene expression in mammals recently.MiRNAs are quite conserved among mammals,while the early microRNAs seem to be more diversified,implying a dynamic functional evolution in the early stage.In this study,the initial function of miRNA was exploited by analyzing the targets of miRNAs on virus system and host genes.Influenza viruses H1N1 and H5N1 were used to infect A549 cells to analyze the regulation of miRNAs on viruses and host genes specifically.The representative 17 species in evolution and 5361 viruses recorded in NCBI were chosed as our study objects.The targets of miRNAs in the 17 species were firstly predicted on viruses and host genes and then on random sequences.By calculating p value and average miRNA target number to analyze miRNA targeting ability.The results showed that the miRNAs from sponge which is a representative of earliest animal showed a high function potential to virus system while other early metazoa kept a lower value.Besides,miRNAs of ancient species tended to have more targets on dsDNA viruses and bacteriophage.Along with evolution,the targeting ability of miRNAs on viruses decreased firstly and increased subsequently,while miRNAs acted more and more specifically on self-genes.These results indicated that miRNAs of early species might mainly function as a component of antiviral mechnism,with the co-evolution of viruses and hosts,miRNAs act more on self-genes and finally serve as an importat regulator for higher organisms.As a consequence,it is a new point of view about the initial function of miRNAs and the function evolution in macroevolution in our work.We also conduct preliminary exploration on the co-regulation of influenza viruses H1N1,H5N1 and host miRNAs to gene expression by small RNA sequencing and gene expression analysis of A549 cells before and after influenza viruses infection.We firstly used miRmat to predict viruses miRNAs and then combined Blastn and RNAhybrid to predict miRNAs targets.Meanwhile,by analysing the differential expression of miRNA and mRNA of A549 cells after infecting by H1N1 and H5N1 and construting regulatory networks,we could explore the gene regulation differences which may cause the different fatality rate of the two viruses.Our study showed that the regulation of miRNA plays an important part in the different fatality rate of viruses.The predicted results of host miRNAs to viruses and statistic analysis showed that genes of viruses with lower fatality rate such as H1N1 were targeted more by host miRNAs.On the contrary,genes of H5N1 with higher fatality rate were not significantly targeted by host miRNAs.Besides,by analyzing the expression of mRNAs,we found more cytokines and immune factors were activated after H5N1 infection,which may cause cytokine storm.These facts implied the expression of more genes were changed after H5N1 infection and its related with miRNAs regulation.Our results showed a wider regulation of miRNAs when defending against influenza viruses.