病毒與宿主相互作用lyx(已修改)
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【正文】 病毒與宿主相互作用 李怡璇 What is a virus ? A virus is a piece of bad news wrapped in protein. — Peter Medawar (191587), Nobel prize winner ? Viruses (from the Latin virus meaning toxin or poison) 1. 體積非常微小，必須用電子顯微鏡才能看到的非細(xì)胞型微生物； 2. 結(jié)構(gòu)簡(jiǎn)單，無(wú)完整細(xì)胞結(jié)構(gòu)，僅有一種核酸（ RNA或 DNA）； 3. 嚴(yán)格的細(xì)胞內(nèi)寄生性，只能在一定種類(lèi)的活細(xì)胞中增殖； 4. 對(duì)抗生素不敏感，但對(duì)干擾素敏感。 Viruses are far smaller than their host cells The Baltimore Classification Why to study virushost interactions？ ? Mechanism: ? The life cycle of viruses ? Viral pathogenesis ? Application: ? Research Tools ? Virotherapy Contents ?Part I: Viruscell Interactions ?Part II: Host immune responses to viral infection Viruscell Interactions The sequential steps in viral infection – Entry – Primary site replication – Spread within the host – Shedding – Transmission Part I Schematic diagram to illustrate possible sites of virus entry into the body. Cycle of infection Secondary sites Spread Entry Shedding Shedding Local Lymphatic Blood (viremia) Neuronal Primary sites Viruscell Interactions ?病毒嗜性（ Viral tropism） 某一病毒感染宿主的細(xì)胞組織特異性； 病毒嗜性也決定病毒感染的宿主范圍。 病毒的感染和復(fù)制部位 ≠發(fā)病或致病部位 ?在病毒大量復(fù)制的部位，病損程度并不一定嚴(yán)重； ?病變嚴(yán)重的部位病毒卻不一定大量復(fù)制。 Part I ?決定病毒嗜性的因素 病毒受體 1. 細(xì)胞表面的受體，為糖蛋白，糖脂，粘多糖等。 2. 不同的病毒采用不同的細(xì)胞受體。 3. 在某些情況下，病毒進(jìn)入細(xì)胞需要多個(gè)受體或共受體的參與。 4. 同一病毒的不同病毒株可能吸附不同的受體。 5. 并非所有表達(dá)病毒受體的細(xì)胞均能支持病毒完成增殖。 6. 細(xì)胞受體在宿主物種間的差異可能限制了病毒的宿主范圍。 ? Molecular backbone cartoons of some glycoprotein viral receptors. Cell 1995, 82:531533. Viral attachment proteints (VAP) A naked virus An enveloped virus Three different types of viruscell surface molecule interactions Models of peration by animal viruses ? Receptor expression is necessary but not sufficient to explain poliovirus tissue tropism. Journal of virology 1992, 66:296304. 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. 2022, 77(16): 8801–8811. The papillomavirus life cycle is tied to epithelial cell differentiation. ? 細(xì)胞表面受體； ? 各種蛋白質(zhì)的細(xì)胞：有利于病毒吸附、復(fù)制、組裝和釋放； ? 其他物理因素：病毒可在細(xì)胞外環(huán)境中生存； ? 宿主免疫反應(yīng)。 決定病毒嗜性的因素（概括） Viruscell Interactions ?Viral tropism ?How do viruses affect cells? Part I 大多數(shù)病毒感染是無(wú)癥狀的 病毒性疾病是一種 “ 不尋常 ” 的感染后果 ? 分子水平變化 ? 細(xì)胞結(jié)構(gòu)改變 ? 細(xì)胞表型改變 ? 信號(hào)途徑 ? DNA復(fù)制 ? 轉(zhuǎn)錄 ? 翻譯 ? 細(xì)胞膜改變 ? 包涵體 ? 細(xì)胞骨架改變 ? 細(xì)胞死亡 ? 細(xì)胞周期抑制 ? 細(xì)胞融合 ? 細(xì)胞轉(zhuǎn)化 ? 穩(wěn)定狀態(tài)感染 Cell molecular responses to viruses ?Responses to viral attachment: activate or block signaling cascade —mimic the normal ligand for the receptors ? The MAPK pathways in vertebrates follow a ?threekinase module‘ model for transmitting signals from the cell surface to the nucleus to execute an appropriate biological response. The MAPK/ERK pathway is presented with its key ponents and the hepatitis virus proteins known to target the pathways are indicated. Virus Res. 2022, 92(2): 131–140. Cell molecular responses to viruses ?Responses to viral attachment: activate or block signaling cascade ?Viral modulation of host cell transcription host genes Downregulatio
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