发热伴血小板减少综合征(新型布尼亚病毒感染)教案资料.ppt

新型布尼亚病毒感染;;布尼亚病毒科 （Bunyaviridae）;布尼亚病毒科;病毒基因组结构与功能 ;;;中国预防医学杂志; 2017,18(6):465;;New England Journal of Medicine， 2011， 364:1523 －1532．;;传染源;传播途径;;*;蜱的活动期比较长，一些蜱传疾病的研究表明，蜱的成虫、若虫和幼虫均可带毒并传播疾病。 蜱的寄生动物种类广泛，主要寄生于牛、马、羊、猪、犬、野兔、刺猬等，饲养和接触寄生蜱的家畜及宠物，可能被蜱叮咬。 ;疾病名称;中国蜱传疾病的分布;易感人群;流行特征;New England Journal of Medicine， 2011， 364:1523 －1532 Virol Sin.2017 ;32(1):51-62 ;Virol Sin.2017 ;32(1):51-62 ;发病机制;Severe fever with thrombocytopenia syndrome phlebovirus (SFTSV), listed in the World Health Organization Prioritized Pathogens, is an emerging phlebovirus with a high fatality1-4. Owing to the lack of therapies and vaccines5,6, there is a pressing need to understand SFTSV pathogenesis. SFSTV non-structural protein (NSs) has been shown to block type I interferon induction7-11 and facilitate disease progression12,13. Here, we report that SFTSV-NSs targets the tumour progression locus 2 (TPL2)-A20-binding inhibitor of NF-κB activation 2 (ABIN2)-p105 complex to induce the expression of interleukin-10 (IL-10) for viral pathogenesis. Using a combination of reverse genetics, a TPL2 kinase inhibitor and Tpl2-/- mice showed that NSs interacted with ABIN2 and promoted TPL2 complex formation and signalling activity, resulting in the marked upregulation of Il10 expression. Whereas SFTSV infection of wild-type mice led to rapid weight loss and death, Tpl2-/- mice or Il10-/- mice survived an infection. Furthermore, SFTSV-NSs P102A and SFTSV-NSs K211R that lost the ability to induce TPL2 signalling and IL-10 production showed drastically reduced pathogenesis. Remarkably, the exogenous administration of recombinant IL-10 effectively rescued the attenuated pathogenic activity of SFTSV-NSs P102A, resulting in a lethal infection. Our study demonstrates that SFTSV-NSs targets the TPL2 signalling pathway to induce immune-suppressive IL-10 cytokine production as a means to dampen the host defence and promote viral pathogenesis.;Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic f