疱疹病毒感染与免疫逃逸--研究生-2015-12 课件.ppt

Alphaherpesviruses Infection and its Evasion of Host Innate Immunity ;Scientific interests;HSV-1逃逸宿主天然免疫/获得性免疫的分子机制； HSV-1与宿主相互作用的分子机制；;自我介绍;Virology;Human Herpes Viruses (HHV);Animal Herpes Viruses (AHV);HSV-1; HSV-1/2: no vaccine available Painful failure of promising genital herpes vaccine. Science.?2010? Phase III trial failure. N Engl J Med. 2012 HSV-1 infection: 100% serum positive latency Pathogenesis: Cold sore, zosteriform skin lesions, pneumonia, systemic infections HSV-1 keratitis (HSK); Blindness Encephalitis/AD: TLR3/UNC93B1/TRAF3/TRIF Stressor: Viral infection (other viruses) Nerve trauma, Physiologic and physical changes Stress, fever, menstruation, and UV light HSV-1 genital infection 60% Gene therapy vector: tumor, neural system diseases, pain ;Varicella Zoster Virus (VZV/HHV3);Core viral DNA Capsid 162 capsomers VP5, VP26, VP23, VP19C;The organization of the HSV-1 genome (152 kb);Immediate early, IE, α regulation of gene transcription Early, E, β transcription factors enzymes Late, L, γ structural proteins;Essential and Accessory Genes;Viral entry;The lytic replication cycle;Three stages of HSV-1 infection;Treatment of HSV-1;Prevention of HSV-1;Host Immunity and Viral Immune Evasion;获得性免疫天然免疫;PRRs and HSV-1/VZV;Toll-like Receptor Signaling;HSV infection and TLR;HSVs interfere with host detection of viral determinants;HSVs interfere with cell viability;HSVs interfere with the induction of type-I interferons and interferon signaling;Adaptive immunity response after HSV-1 infection ; 结构和非结构蛋白作为靶分子 囊膜蛋白：gB、gC、gD、gE、gH 衣壳和皮层蛋白：VP11/12、VP13/14、VP16、VP22、VP5 非结构蛋白：dUTPase和ICP8 ; CTL IFN-γ Granzyme B CD8+T细胞：潜伏感染的维持 三叉神经节周围大量存在，监视 潜伏状态病毒使其不被激活; 由膜蛋白(糖蛋白)诱导产生 中和抗体：鉴别HSV-1/HSV-2 中和抗体：原发感染、再感染 中和抗体：对病毒的免疫逃逸起促进作用; I 型干扰素 （IFN-α/β） 自然杀伤细胞 （NK） 巨噬细胞 （M?） 树突状细胞 （DC） 中性粒细胞等;I 型干扰素;自然杀伤细胞(NK); 直接吞噬入侵的病毒 通过其表面Fc受体吞噬各种病毒复合物 分泌精氨酸酶抑制病毒复制 降解邻近感染细胞中病毒复制必需的精氨