病毒与宿主相互作用研究.pptVIP

病毒与宿主相互作用 李怡璇 What is a virus ? Viruses are far smaller than their host cells Why to study virus-host interactions？ Mechanism: The life cycle of viruses Viral pathogenesis Application: Research Tools Virotherapy Contents Part I: Virus-cell Interactions Part II: Host immune responses to viral infection Virus-cell Interactions The sequential steps in viral infection Entry Primary site replication Spread within the host Shedding Transmission Schematic diagram to illustrate possible sites of virus entry into the body. Virus-cell Interactions 病毒嗜性（Viral tropism） 某一病毒感染宿主的细胞组织特异性；病毒嗜性也决定病毒感染的宿主范围。 病毒的感染和复制部位≠发病或致病部位 在病毒大量复制的部位，病损程度并不一定严重； 病变严重的部位病毒却不一定大量复制。 决定病毒嗜性的因素 病毒受体 细胞表面的受体，为糖蛋白，糖脂，粘多糖等。 不同的病毒采用不同的细胞受体。 在某些情况下，病毒进入细胞需要多个受体或共受体的参与。 同一病毒的不同病毒株可能吸附不同的受体。 并非所有表达病毒受体的细胞均能支持病毒完成增殖。 细胞受体在宿主物种间的差异可能限制了病毒的宿主范围。 Molecular backbone cartoons of some glycoprotein viral receptors. Cell 1995, 82:531-533. Viral attachment proteints (VAP) Three different types of virus-cell surface molecule interactions Models of penetration by animal viruses Receptor expression is necessary but not sufficient to explain poliovirus tissue tropism. Journal of virology 1992, 66:296-304. Other determinants of tropism Activation of viral attachment or fusion proteins by host proteases Cellular transcription factors Temperature sensitivity of virion pH lability of virion Anatomical barriers Host innate and acquired immune response Schematic representation (approximately to scale) of the viral fusion proteins of six different virus families. J Virol. 2003, 77(16): 8801–8811. The papillomavirus life cycle is tied to epithelial cell differentiation. 决定病毒嗜性的因素（概括） 细胞表面受体； 各种蛋白质的细胞：有利于病毒吸附、复制、组装和释放； 其他物理因素：病毒可在细胞外环境中生存； 宿主免疫反应。 Virus-cell Interactions Viral tropism How do viruses affect cells? 分子水平变化 细胞结构改变 细胞表型改变 Cell molecular responses to viruses Responses to viral attachment: activate or block signaling cascade —mimic the normal ligand fo