Highly Pathogenic Avian Influenza Virus H7N7Infection Of Human A549Cells And Investigation On Systems Biology Of Evolutional Network Of Mirna-tf Co-regulated In Pathogenesis Mechanism

Avian Influenza is an infectious disease caused by avian influenza A virus and is dividedinto low pathogenic avian influenza (LPAIV) and high pathogenic avian influenza (HPAIV)depending on difference of pathogenicity to chicken. Besides avian influenza virus mayreassemble in the process of copying so that it could change its structure and be spread tohuman beings. In2003HPAIV H7N7virus outbroke in Holland and caused severe economiclosses and the emergence of fatal cases. MiRNA is an endogenous non-coding single-strandRNA. It plays a role in negative regulation at the post-transcriptional level in distinct mannersvia combination with target genes. Transcription factors start gene transcription throughbonding with cis-acting elements and promote the expression of suppressor gene. MiRNA andtranscription factors jointly regulate the expression of genes in different stages of transcription.Therefore exploring coactions of miRNA and transcription factors in the pathological state ofHPAIV is meaningful to the prevention and cure of diseases.One method was discussed in Chapter1in the paper to make up the co-regulatingnetwork model of miRNA-TF of A549cells from H7N7virus infected persons. Differentiallyexpressed miRNA in pathological state was used as the point of departure and regulationinformation on miRNA and gene was obtained via target prediction. Regulation informationon transcription factor and gene was received through the database. The co-regulatingnetwork model of miRNA-TF was finally obtained through the certain calculating method. Itshowed that it was functionally correlative via the comment and validation of GO. Later onvia documentary validation it showed that connections in regulation network was verified byexperiments under the occurrence of other diseases. Compared with traditional researchmethods in the regulation of miRNA and transcription factors in morbid state, our methodpossesses the following advantages：At first our research method starts with differentiallyexpressed miRNA in pathological state and possesses clear direction. Secondly miRNA,transcription factors and genes involved in regulating network model possess more than3~4nodes in traditional cyclic structure and are more suitable to exploring of complex regulationof miRNA and transcription factors in morbid state.As the agent of vital movement proteins play an important role in the functions and metabolism of creatures and the onset of diseases via interaction among proteins and theircontinuous changes. Besides predictive research on protein functions showed thatinteractional proteins was functionally correlative, namely the function of a protein wasknown and its interactional protein would function in the similar way. The interaction of someother proteins in cells was transient and unstable, thus it was hardly found by researchmethods based on experiments and, however, analysis based on bioinformatics made up forthe shortage. Methods in bioinformatics were applied in the second section in the paper anddifferentially expressed miRNA in morbid state was as the point of departure. Proteinsmediated by host miRNA in various time points（0h，4h，8h，24h，48h，72h）mutually formedthe network after making up avian influenza H7N7virus and key proteins were extractedfrom the protein network. The network was validated and analyzed. The results showed thatthe network was significantly meaningful in biology. The discovery of key proteins in theprocess of change and researches on protein functions was meaningful to host infected H7N7virus.