Pathogenicity And Transmission Of H1N1 Influenza Virus Based On Bioinformatics

Influenza virus is a kind of RNA virus which can bring about influenza tohumans, mammals and birds. It can cause acute respiratory infections and manycomplications because of high infectious and rapid spread, which is a serious threat tohuman health. Influenza viruses can be divided into three types of A, B and C, A-tpyeinfluenza virus has a strong pathogenicity and spreads rapidly, easily lead to pandemic.Outbreak in Mexico in 2009, causing a global pandemic of H1N1 influenza virus isone of them. At present, we can vaccinate to prevent influenza, but the high variabilityof influenza viruses makes it impossible to accurately predict upcoming pandemicvirus subtype, then we can not be targeted for preventive vaccination. On the otherhand, antigenic shift occurs in influenza viruses every decade or so, transforming to novaccine strains, bringing big difficulties to traditional prevention and treatment. So atpresent, the study of pathogenicity and transmission of influenza virus, improving theprevention and treatment of influenza virus, both of them are hot topics of medicalresearch.The accomplishment at genetic sequencing on the RNA fragments of influenzavirus and the establishment at public database virus provide a viable condition to theinfluenza virus research at the gene level. Meanwhile the bioinformatics technicaldevelopment lay an academic foundation for the influenza virus research at the genelevel. MicroRNA-based bioinformatics research is a kind of method of H1N1influenza virus. Through combined with the target gene, microRNA can degeneratetarget mRNA, or inhibit its translation, and then serve a function to regulate geneexpression. Host microRNA can regulate viral gene expression and those microRNAsregulation on the virus can affect its pathogenicity and transmission.In this paper, the research objects are microRNA encoded based on humans andH1N1 influenza virus. We collected each 20 strains of H1N1 influenza virus in 2007,2008, 2009 from NCBI database, and also including 904 strains of mircoRNA encodedbased on humans from miRBase database. We extracted exact matched sequence frommicroRNA seed region encoded based on humans, compared separately with HA, NA, NP, PA, PB2 gene from H1N1 influenza virus, using microRNA screening algorithmcombined with microRNA conservative design, to predict microRNA encoded basedon humans, which can regulate H1N1 influenza virus. We found the microRNA targetgenes which can regulate H1N1 influenza virus though the forecasting software ofRNA22 microRNA target detection, and then made a further test to the predictedmicroRNA according to the forecast results of the target gene. By the regulatevariation of mircoRNA and target genes, we analysis human encoded microRNA'saffect to the pathogenicity and transmission of H1N1 influenza virus.The major resultsobtained in this study are as follows:(1) We extracted exact matched sequence from microRNA seed region encodedbased on humans, compared separately with HA, NA, NP, PA, PB2 gene from H1N1influenza virus. Extracted each 20 strains from HA gene, NA gene, NP gene, PA gene,PB2 gene of H1N1 influenza virus in 2007, 2008,2009, we separately made an exactmatched sequence alignment with 904 strains of human encoded mircoRNA seedregion. The results are as follows: In 2007, there are 62 exact matched HA gene, 43matched NA gene, 47 matched NP gene, 80 matched PA gene, 70 matched PB2 gene.In 2008, there are 58 exact matched HA gene, 44 matched NA gene, 51 matched NPgene, 69 matched PA gene, 67 matched PB2 gene. In 2009, there are 84 exact matchedHA gene, 66 matched NA gene, 50 matched NP gene, 102 matched PA gene, 99matched PB2 gene.(2) We predicted human encoded microRNA, which can regulate H1N1 influenzavirus by microRNA screening algorithm combined with microRNA conservativedesign. With this prediction algorithm, we got the microRNA genes which canregulation of influenza virus H1N1; there are 19 HA gene, 22 NA genes, 13 NP genes,31 PA genes and 33 PB2 genes.(3) Through the target gene prediction software, according to the conservativecontrol on target sites by microRNA, we got microRNA with correspondent targetgene. There two microRNA which can regulate HA gene, hsa-miR-711; one regulatesNA gene, hsa-miR-581; four regulate PA gene, hsa-miR-1248, hsa-miR-1274b,hsa-miR-130b*and hsa-miR-875-3p; seven regulate PB2 gene, hsa-miR-29b-2*,hsa-miR-578, hsa-miR-1208, hsa-miR-569, hsa-miR-2117 and hsa-miR-942andhsa-miR-375.The research of this paper suggests that human encoded microRNA has theability to regulate H1N1 influenza virus. The predicted microRNA only corresponds to a gene fragment of influenza virus, and most of them only affect the same target genein H1N1 influenza virus, there are also small numbers affect more than a fragment ofthe target gene in influenza virus. HA gene in H1N1 influenza virus has someconnection with virus'pathogenic, comparing with affecting in 2009, microRNAhsa-miR-711 which affects HA gene fragment corresponding to the target gene inH1N1 influenza virus, has a significantly lower free energy than in 2008 and in 2007,the number of base pairing at the corresponding target genes in 2009 are higher thanthat in 2008 and 2007. It suggests that in 2009 microRNA hsa-miR-711 has a strongerregulated ability on HA gene in H1N1 influenza virus than in 2008 and in 2007. So wespeculate that it's one of the reasons caused the decreased pathogenicity in H1N1influenza virus in 2009. NA gene in H1N1 influenza virus has some connection withvirus'diffusion and dissemination, comparing with affecting in 2009, microRNAhsa-miR-581 which affects NA gene fragment corresponding to the target gene inH1N1 influenza virus, has a significantly higher free energy than in 2008 and in 2007.It suggests that in 2009 microRNA hsa-miR-581 has a poor regulated ability on NAgene in H1N1 influenza virus than in 2008 and in 2007. So we speculate that it's oneof the reasons caused the strong transmission in H1N1 influenza virus in 2009.