严重发热没伴血小板减少综合征病毒(sftsv)与宿主先天免疫相互作用的初步研究-病原生物学专业毕业论文.docxVIP

中国医学科学院北京协和医学院硕士研究生学位论文Severe 中国医学科学院北京协和医学院硕士研究生学位论文 Severe fever with thrombocytopenia syndrome virus activates host innate immunity and inhibits exogenous TypeI IFN signaling pathway through its NS protein Background：Severe Fever wim thrombocytopenia syndrome virus(SFTSV)was first reported in 2009 in China．Clinically SFTSV infection，the result of tick biting mainly occurred in rural areas causes fever,thrombocytopenia and gastrointestinal symptoms． With mortality rate of 1 0％-30％，no specific drug treatment for SFTSV infection， although ribavirin is commonly prescribed to relieve the symptomes．In addition，the pathogenic mechanism of SFTSV is still not well understood．Current research is designed to explore the interactions between SFTSV and host innate immune responses． objective：To observe the effect of SFTSV on host innate immune responses；to observe the influence of SFTSV and its Non—Structural fNS)protein on exogenous Type I IFN signaling pathway． Methods：First，we used the whole blood of a patient infected with SFTSV to infect Vero cells to prepare the vims stock；Then SFTSV Was used to infect Hela,Huh7．0，and Huh7．5．1 to see whether these cells support SFTSV replication or not；To study whether SFTSV infection could activate the host innate immune responses，IFNGt，ⅢNp and the ISG expression were determined by Realtime PCR following SFTSV infection in these cells；To study the effect of SFTSV and its NS protein on exogenous IFNa-induced Jak／STAT signaling，P—STAT I(Western Blot)，ISRE activity(Dural-luciferase reporter assay)and ISGs(real-time PCR)were examined following SFTSV infection or NS over-expression in the presence of IFNa． Results：SFTSV Can infect Vero，Hela，Huh7．0，and Huh7．5．1 cells successfully；SFTSV Can activate host innate immune responses in Hela cells as shown by the increased IFNa／p production together with up-regulation of TLR-3，RIG—I in Hela cells following SFTSV infection．Interestingly,WNa／p was not increased in both Huh7．0 and Huh7．5．1