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1、Viral Genetics and Variation 病毒的遗传与变异,Conceptions,Genetics遗传: After virus replicates , the characters on the progeny virus are similar with the previous generation. Variation变异: After virus replicates , the characters on the progeny virus are different with the previous generation.,一、 Variation mech
2、anism 病毒变异的机制,Heritable variation遗传型变异 因病毒遗传物质核酸发生了改变，导致其变异后的性状可遗传给子代病毒。 Non- Heritable variation非遗传型变异 又称基因产物的相互作用，因病毒核酸并未发生改变，所以此变异一般不能遗传。,（一） Heritable variation 遗传型变异,Virulence changes Conditional lethal mutant 条件致死突变株 eg. temperature sensitive (ts) mutant Host-range mutant (hr) 宿主范围突变株 Drug-res
3、istant mutant 耐药突变株,1、Gene Mutation 基因突变,Recombination 两个病毒基因组间核酸序列交换、组合 Reassortment ( segmented genomes) RNA viruses: influenza virus 分节段的RNA病毒基因组之间，通过基因片段交换使子代基因组发生突变 病毒基因组与细胞基因组之间的重组,2 、Recombination / Reassortment 重组与重配,3 、integration整合,（二） Non-Heritable variation 非遗传型变异,Interactions：when two g
4、enetically distinct viruses infect a cell. 4 different phenomena can ensue继发 （1） Phenotypic mixing or transcapsidation 表型混合与核壳转移 （2）genotype mixing 基因型混合 （3）enhancement 增强 （4）complementation 互补,(1) Phenotypic mixing表型混合,The genome of virus A can be coated with the surface protein of virus type B 两株病
5、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壳或包膜包裹，不是遗传物质的交换，而是基因产物的交换 transcapsidation核壳转移： 无包膜病毒发生的表型混合,(2)genotype mixing 基因型混合,Genome A + genome B same capsid衣壳 Capsid A + capsid B same envelope包膜 实质：核酸未重组合，没有遗传性,(3)enhancement 增强 两病毒混合培养，一病毒能增强另一病毒的产量,(4)complementation互补,Classification of Viruses 病毒的分类,国
6、际病毒分类委员会ICTV,By 2001 -66 families科, 9 subfamilies亚科 -244 genera属 For humans and animals -24 families, -DNA: 7; RNA: 17 for humans,basis of classification 病毒分类依据,Virion structure and proteries病毒结构与性质 Virion morphology and size病毒大小和形态 Symmetry of nucleocapsids 核衣壳对称性 Envelope 有无包膜 Physicochemical prop
7、erties 理化特性 Antigenic properties抗原性 Biologic properties生物学特性,Viroids(类病毒),Viroids are small (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 (250-400nt),杆状 RNA 分子，有二级结构 无衣壳或包膜 在核内增殖，
8、严格细胞内寄生 多与植物疾病相关,satellites卫星病毒 / Virosid拟病毒,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,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
9、克雅病（亚急性海绵状脑病） in humans, scrapie痒病in sheep & bovine spongiform encephalopathy (BSE)牛海绵状脑病in cattle.,Chapter 19,Viral Infection and Immunity,病毒的感染与免疫,This chapter will focus on,Conceptions Horizontal and Vertical transmission水平传播及垂直传播, inapparent and apparent infection隐性感染及显性感染, Persistent viral infe
10、ction持续性病毒感染， Latent infection潜伏性感染, Chronic infection慢性感染, Slow virus infection慢发病毒感染, Inclusion body包涵体 Questions Describe the types and routes of viral infection. What is interferon干扰素? List the bioactivities of it?,Section 1 Viral Infection 病毒的感染,Viral infection: the process of virus entering an
11、d 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.,a. A particular disease may be caused by several viruses that have a common tissue tropism取向 (preference选择). e.g., HAV, HBV, HCV, HDV, HEV, etc hepat
12、itis. 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,Respiratory tract 痰、唾液、飞沫、气溶胶 Alimentary tract 饮水
13、、食物 Skin 动物咬伤、昆虫叮咬 Blood 输血、注射、针刺、器官移植 Genital tract 性交 Urinary tract 洗浴 placenta, birth canal 孕期、分娩,I. tract of viral infection 感染途径,II. Modes of viral transmission 传播方式,Horizontal transmission水平传播: direct host-to-host transmission of viruses. 人与人不同个体间的传播 Vertical transmission垂直传播: the transmission
14、 of viruses from parent to the young via placenta, birth canal. 亲代通过胎盘或产道传给子代,Local infection Systemic infection Direct contact ：细胞细胞 blood：侵入部位血液 neural system：感染部位神经元,III. Routes of transmission 播散方式, Unapparent infection 隐性感染 (subclinical infection): Virus multiply in the host cells without causi
15、ng 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,Viruses multiply in host cells and cause clinical symptoms. Acute infection 急性病毒感染: short incubation, sudden on
16、set, and short duration of disease (several days to weeks); e.g., common cold, influenza, hepatitis A. Persistent viral infection 持续性病毒感染: viruses persist in the host for long time period, several months or years or decades ，sometimes for the whole life., Apparent infection 显性感染,Latent infection: Vi
17、ruses 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 produce clinical symptoms. E.g. HSV-1 Chronic infection: After acute infection, viruses are not eliminated and there is intermittent间歇的
18、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. Slow virus infection / delay infection: possess a prolonged incubation period lasting months or years after viral infection, during which no clinical
19、 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 infection with rare late complication),Persistent infection: includes,herpes labialis 唇疱疹 by reactivated HSV,HSV-1 esta
20、blishes latent infection and can recur 重现 from the trigeminal ganglia. 三叉神经节,A、Direct virus-host cell interaction对宿主细胞直接作用 Cytocidal infection 溶细胞型感染 Steady state infection 稳定状态感染 Cell apoptosis 细胞凋亡 e.g., HSV Viral genes integrate into cellular chromosome整合 e.g., EBV, HIV. Cell hyperplasia 增生 and c
21、ell transformation 转化 Inclusion body 形成包涵体 B、 Virus-induced immunopathology免疫病理作用 Humoral immune effect Cell immune effect Viruses destroy immune system e.g., HIV destroy CD4+TC Self-immune disease,V、Mechanisms for viral infection: 病毒感染机制,1、 Cytocidal infection 溶细胞型感染 viral replication cause cell de
22、ath; naked virus infection; e.g. poliovirus脊髓灰质炎病毒, adenovirus. Mechanism: block synthesis of cellular macromolecules； produce and accumulate toxic viral proteins ； destroy 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 lysi
23、s,2、Steady state infection 稳定状态感染 enveloped viruses infection; little destruction of cells. Alteration of host cell membrane.,3、Apoptosis 细胞凋亡 cell programmed death 4、Integration infection 整合 Integration: Viral DNA integrates into cellular chromosome,Budding,5、Cell hyperplasia 增生 and cell transforma
24、tion 转化,Cell hyperplasia 增生 : 病毒不仅不抑制宿主细胞DNA合成反而促进 cell transformation 转化： 病毒感染后使宿主细胞形态发生变化,6、 Inclusion body 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
25、 diagnosis ：. E.g., Negri body for rabies virus,Negri body of rabies virus in infected neuron,H&E-stained tissue,(intra-cytoplasmic),Humoral immunopathology New AgsAg-Ab complement Ag-Ab complex deposit Cell-mediated immunopathology New Ags induce cytotoxic effect. Virus-induced immunosuppression (e
26、.g., HIV, measles virus, rubella virus风疹病毒 ) autoimmune response ：against to self-cell .,B. Virus-induced immunopathology,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 p
27、roduced by T cell Two types: () (),Section 2 Anti-virus immune,Interferon (IFN)干扰素：,Bioactivity of IFNs:,Antiviral effects: block synthesis of viral proteins. Immuno-modulatory 调节effects: stimulate NK cells and macrophages activity to kill abnormal cells. Antitumor effects: regulate oncogene致癌基因expr
28、ession, and inhibit tumor cell mitosis有丝分裂.,Viral infection or IFN inducers activate IFN genes; IFN genes are transcribed and translated into IFNs. IFNs bind to the receptors on the neighboring cells, and activate cellular genes to produce antiviral proteins (AVP) which can inhibit viral protein synthesis. IFN action is species-specific, but not virus specific.,mechanism of IFN action:,Viral infection,Activate IFN gene,IFN synthesis,IFN release,IFN receptor,Activate AVP genes,AVP production,Inhibit viral protein synthesis,