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1、病毒的遗传与变异本讲稿第一页，共三十八页ConceptionsoGenetics遗传遗传:After virus replicates,the characters on the progeny virus are similar with the previous generation.oVariation变异变异:After virus replicates,the characters on the progeny virus are different with the previous generation.本讲稿第二页，共三十八页一、一、Variation mechanism 病毒
2、变异的机制病毒变异的机制oHeritable variation遗传型变异遗传型变异 因病毒遗传物质因病毒遗传物质核酸核酸发生了发生了改变改变，导致其，导致其变异后的性状可遗传给子代病毒。变异后的性状可遗传给子代病毒。oNon-Heritable variation非遗传型变异非遗传型变异 又称又称基因产物基因产物的相互的相互作用作用，因病毒核酸并，因病毒核酸并未发生改变，所以此变异一般不能遗传。未发生改变，所以此变异一般不能遗传。本讲稿第三页，共三十八页（一）（一）Heritable variation 遗传型变异遗传型变异oVirulence changeso Conditional le
3、thal mutant 条件致死突变株条件致死突变株 eg.temperature sensitive(ts)mutanto Host-range mutant(hr)宿主范围突变株宿主范围突变株oDrug-resistant mutant 耐药突变株耐药突变株1、Gene Mutation 基因突变基因突变本讲稿第四页，共三十八页oRecombination 两个病毒基因组间核酸序列交换、组合两个病毒基因组间核酸序列交换、组合oReassortment(segmented genomes)RNA viruses:influenza virus 分节段的分节段的RNA病毒基因组之间，通过基病毒
4、基因组之间，通过基因片段交换使子代基因组发生突变因片段交换使子代基因组发生突变o病毒基因组与细胞基因组之间的重组病毒基因组与细胞基因组之间的重组2、Recombination/Reassortment 重组与重配重组与重配 3、integration整合整合本讲稿第五页，共三十八页（二（二）Non-Heritable variation 非遗传型变异非遗传型变异oInteractions：when two genetically distinct viruses infect a cell.4 different phenomena can ensue继发继发（1）Phenotypic mix
5、ing or transcapsidation 表型混合与核壳转移表型混合与核壳转移（2）genotype mixing 基因型混合基因型混合（3）enhancement 增强增强（4）complementation 互补互补本讲稿第六页，共三十八页(1)Phenotypic mixing表型混合表型混合oThe genome of virus A can be coated with the surface protein of virus type B 两株病毒共同感染同一细胞时，一种病毒两株病毒共同感染同一细胞时，一种病毒复制的核酸被另一病毒所编码的蛋白质衣复制的核酸被另一病毒所编码的蛋
6、白质衣壳或包膜包裹，不是遗传物质的交换，而壳或包膜包裹，不是遗传物质的交换，而是基因产物的交换是基因产物的交换otranscapsidation核壳转移：核壳转移：无包膜病毒发生的表型混合无包膜病毒发生的表型混合 本讲稿第七页，共三十八页(2)genotype mixing 基因型混合基因型混合oGenome A+genome B same capsid衣壳衣壳oCapsid A+capsid B same envelope包膜包膜o实质：核酸未重组合，没有遗传性实质：核酸未重组合，没有遗传性(3)enhancement 增强增强两病毒混合培养，一病毒能增强另一病两病毒混合培养，一病毒能增强另
7、一病毒的产量毒的产量本讲稿第八页，共三十八页(4)complementation互补互补本讲稿第九页，共三十八页Classification of Viruses病毒的分类病毒的分类本讲稿第十页，共三十八页国际病毒分类委员会ICTVn nBy 2001 -66 families科,9 subfamilies亚科 -244 genera属nFor humans and animals -24 families,-DNA:7;RNA:17 for humans本讲稿第十一页，共三十八页basis of classification 病毒分类依据病毒分类依据n nVirion structure a
8、nd proteries病毒结构与性质病毒结构与性质n nVirion morphology and size病毒大小和形态病毒大小和形态n nSymmetry of nucleocapsids 核衣壳对称性核衣壳对称性n nEnvelope 有无包膜有无包膜n nPhysicochemical properties 理化特性理化特性n nAntigenic properties抗原性抗原性n nBiologic properties生物学特性生物学特性本讲稿第十二页，共三十八页本讲稿第十三页，共三十八页本讲稿第十四页，共三十八页 Viroids(类病毒类病毒)Viroids are smal
9、l(250-400nt,Nucleotide),RNA molecules with a rod-like secondary structure，which possess no capsid or envelope，which are associated with certain plant diseases.很小很小(250-400nt),杆状杆状 RNA 分子，有二级结构分子，有二级结构无衣壳或包膜无衣壳或包膜 在核内增殖，严格细胞内寄生在核内增殖，严格细胞内寄生 多与植物疾病相关多与植物疾病相关本讲稿第十五页，共三十八页satellites卫星病毒卫星病毒/Virosid拟病毒拟病
10、毒特点：1 是RNA病毒，500-2000bp 2 复制需要辅助病毒 3 与辅助病毒基因无同源性 4 所致疾病与辅助病毒无关有两类：一类可编码自身衣壳蛋白 另一类为卫星病毒RNA分子本讲稿第十六页，共三十八页Prions 朊粒 consist of a single type of protein molecule with no nucleic acid component.These agents are associated with diseases such as Creutzfeldt-Jakob disease克雅病（亚急性海绵状脑病）in humans,scrapie痒病in
11、sheep&bovine spongiform encephalopathy(BSE)牛海绵状脑病in cattle.本讲稿第十七页，共三十八页Chapter 19Viral Infection and Immunity 病毒的感染与免疫病毒的感染与免疫本讲稿第十八页，共三十八页This chapter will focus onoConceptionsHorizontal and Vertical transmission水平传播及垂直传播水平传播及垂直传播,inapparent and apparent infection隐性感染及显性感染隐性感染及显性感染,Persistent vira
12、l infection持续性病毒感染，持续性病毒感染，Latent infection潜伏性感染潜伏性感染,Chronic infection慢性感染慢性感染,Slow virus infection慢发病毒感染慢发病毒感染,Inclusion body包涵体包涵体 oQuestionsnDescribe the types and routes of viral infection.nWhat is interferon干扰素干扰素?List the bioactivities of it?本讲稿第十九页，共三十八页Section 1 Viral Infection 病毒的感染病毒的感染Vi
13、ral infection:the process of virus entering and multiplying in the human or animal body.病毒侵入人及动物机体并在其中增殖的过程Viral pathogenesis:the interaction between viral&host factors that leads to disease.本讲稿第二十页，共三十八页a.A particular disease may be caused by several viruses that have a common tissue tropism取向(pref
14、erence选择).e.g.,HAV,HBV,HCV,HDV,HEV,etc hepatitis.b.A particular virus may cause several different diseases or no observable引人注意的 symptoms.e.g.,HSV单纯疱疹病毒-1pharyngitis咽炎,herpes labialis 唇疱疹，genital herpes生殖道疱疹,encephalitis脑炎,keratoconjunctivitis角膜结膜炎.The characteristic of viral infection本讲稿第二十一页，共三十八页
15、nRespiratory tract 痰、唾液、飞沫、气溶胶nAlimentary tract 饮水、食物nSkin 动物咬伤、昆虫叮咬nBlood 输血、注射、针刺、器官移植nGenital tract 性交nUrinary tract 洗浴nplacenta,birth canal 孕期、分娩I.tract of viral infection 感染途径本讲稿第二十二页，共三十八页II.Modes of viral transmission 传播方式nHorizontal transmission水平传播水平传播:direct host-to-host transmission of vi
16、ruses.人与人不同个体间的传播 n Vertical transmission垂直传播垂直传播:the transmission of viruses from parent to the young via placenta,birth canal.亲代通过胎盘或产道传给子代本讲稿第二十三页，共三十八页nLocal infection Systemic infectionn Direct contact：细细胞胞细细胞胞n blood：侵入部位：侵入部位血液血液n neural system：感染部位神经元：感染部位神经元III.Routes of transmission 播散方式本讲
17、稿第二十四页，共三十八页n Unapparent infection 隐性感染隐性感染(subclinical infection):Virus multiply in the host cells without causing clinical symptoms or causing mild symptoms.Significance:important source of infection;重要传染源 acquire immunity;获得免疫力 misdiagnose or fail to diagnose;易误诊和漏诊IV、Types of infection 感染类型本讲稿第二
18、十五页，共三十八页Viruses multiply in host cells and cause clinical symptoms.Acute infection 急性病毒感染急性病毒感染:short incubation,sudden onset,and short duration of disease (several days to weeks);e.g.,common cold,influenza,hepatitis A.Persistent viral infection 持持续续性病毒感染性病毒感染:viruses persist in the host for long t
19、ime period,several months or years or decades，sometimes for the whole life.n Apparent infection 显性感染显性感染本讲稿第二十六页，共三十八页oLatent infection:Viruses persist in the host in a hiding form and there is no production of infectious viruses.Under some conditions,the latent viruses are activated and multiply to
20、 produce clinical symptoms.E.g.HSV-1oChronic infection:After acute infection,viruses are not eliminated and there is intermittent间歇的multiplication and shedding排出 of viruses.Virus can be continuously detected;often mild,or no clinical symptoms.E.g.HBV cause chronic hepatitis B.oSlow virus infection/d
21、elay infection:possess a prolonged incubation period lasting months or years after viral infection,during which no clinical symptoms appear but the infectious viruses may multiply,then chronic and progressive diseases appear and eventually develop into fatal infections.E.g.,Measles virus SSPE (acute
22、 infection with rare late complication)Persistent infection:includes本讲稿第二十七页，共三十八页 herpes labialis 唇疱疹唇疱疹 by reactivated HSVHSV-1 establishes latent infection and canrecur 重现重现 from the trigeminal ganglia.三叉神经节本讲稿第二十八页，共三十八页A、Direct virus-host cell interaction对宿主细胞直接作用nCytocidal infection 溶细胞型感染nSte
23、ady state infection 稳定状态感染nCell apoptosis 细胞凋亡 e.g.,HSVnViral genes integrate into cellular chromosome整合 e.g.,EBV,HIV.nCell hyperplasia 增生 and cell transformation 转化nInclusion body 形成包涵体B、Virus-induced immunopathology免疫病理作用nHumoral immune effect nCell immune effect nViruses destroy immune system e.g
24、.,HIV destroy CD4+TC nSelf-immune disease V、Mechanisms for viral infection:病毒感染机制本讲稿第二十九页，共三十八页 1、Cytocidal infection 溶细胞型感染溶细胞型感染 viral replication cause cell death;onaked virus infection;e.g.poliovirus脊髓灰质炎病毒,adenovirus.oMechanism:nblock synthesis of cellular macromolecules；nproduce and accumulate
25、 toxic viral proteins；ndestroy organelles.e.g.lysosome permeability溶酶体膜通透性 cell autolyze细胞自溶；A.Direct interaction between viruses and host:Host cell lysis本讲稿第三十页，共三十八页 2、Steady state infection 稳定状态感染稳定状态感染oenveloped viruses infection;olittle destruction of cells.oAlteration of host cell membrane.3、A
26、poptosis 细胞凋亡细胞凋亡 cell programmed death4、Integration infection 整合整合o Integration:Viral DNA integrates into cellular chromosome Budding本讲稿第三十一页，共三十八页5、Cell hyperplasia 增生增生 and cell transformation 转化转化Cell hyperplasia 增生增生:病毒不仅不抑制宿主细胞病毒不仅不抑制宿主细胞DNA合成反而促进合成反而促进cell transformation 转化：转化：病毒感染后使宿主细胞形态发生变
27、化病毒感染后使宿主细胞形态发生变化6、Inclusion body 包涵体包涵体 The round or oval structures in the cytoplasm or nucleus,or both,acidophilic or basophilic which can be observed in some infected cells under light microscope.Significance：laboratory diagnosis：.E.g.,Negri body for rabies virus本讲稿第三十二页，共三十八页Negri body of rabie
28、s virus in infected neuron H&E-stained tissue(intra-cytoplasmic)本讲稿第三十三页，共三十八页nHumoral immunopathologyoNew AgsAg-Ab complementoAg-Ab complex depositnCell-mediated immunopathology oNew Ags induce cytotoxic effect.nVirus-induced immunosuppression (e.g.,HIV,measles virus,rubella virus风疹病毒)nautoimmune r
29、esponse：against to self-cell.B.Virus-induced immunopathology本讲稿第三十四页，共三十八页 host-encoded proteins which can inhibit viral replication.It can be produced by macrophages、lymphocyte、somatic cell.For human:produced by leucocyte produced by fibroblast produced by T cell Two types:()()Section 2 Anti-virus
30、immune Interferon(IFN)干扰素：干扰素：本讲稿第三十五页，共三十八页Bioactivity of IFNs:oAntiviral effects:block synthesis of viral proteins.oImmuno-modulatory 调节effects:stimulate NK cells and macrophages activity to kill abnormal cells.oAntitumor effects:regulate oncogene致癌基因expression,and inhibit tumor cell mitosis有丝分裂.本
31、讲稿第三十六页，共三十八页nViral infection or IFN inducers activate IFN genes;nIFN genes are transcribed and translated into IFNs.nIFNs bind to the receptors on the neighboring cells,and activate cellular genes to produce antiviral proteins(AVP)which can inhibit viral protein synthesis.nIFN action is species-specific,but not virus specific.mechanism of IFN action:本讲稿第三十七页，共三十八页Viral infectionActivate IFN geneIFN synthesis IFN releaseIFN receptor Activate AVP genes AVP productionInhibit viral protein synthesis 本讲稿第三十八页，共三十八页