病毒学总论.doc

病毒的基本性状病毒的结构和化学组成一 结构-nucleocapsid1.core 基因组2.capsid 抗原性-envelopeSpikes(刺突) - virus-encoded glycoprotein protruding from lipid bilayer, which are important for adsorption and entry into the host cell.二 化学组成与功能-病毒核酸1. Segmented RNA: A few virusescontainsegmentedRNAgenome.Influenzavirus： 7- 8segmentsRotavirus轮状病毒 : 11 segmentsHemorrhagic fever virus : 3 segments2. Infectious nucleic acidInfectious nucleic acid is purified viral DNA or RNA (without any protein) that can carry out the entite viral growth cycle and result in the production of complete virus particles in host cells. Such as the genomes of dsDNA viruses and +ssRNA viruses.3. Functions1) to direct the virus replication2) viral genome（基因组): viral nucleic acid conteins all genetic information of the virus. 3) some of viral nucleic acid possess infectiousness - infectious nucleic acid -病毒蛋白质viral attachment proteins(VAP) 能与宿主细胞表面受体结合的蛋白质称为病毒吸附蛋白，VAP与受体的相互作用决定了病毒感染的组织亲嗜性，如与红细胞结合的VAP称为血凝素hemagglutinin(HA).-脂类和糖脂质主要存在于包膜，有些病毒含少量糖类，以糖蛋白形式存在，也是包膜的表面成分之一。包膜的主要功能是维护病毒体结构的完整性，失去包膜的包膜病毒没有感染性。病毒的增殖-病毒的复制周期1. Absorption病毒VAP宿主细胞的受体甲型流感病毒HA唾液酸HIVGp120CD42. Penetration Endocytosis(naked), fusion(enveloped), 直接穿入3. Uncoating 溶酶体酶4. Biosynthesis1) dsDNA 2) +ssRNA 3) retrovirus5.assembly and release(组装DNA核，RNA质；释放裸露lysis，包膜budding)病毒的遗传与变异一 基因突变Conditional lethal mutant: the virus proliferation only occur under certain conditions.Temperature-sensitive mutant ( ts mutant ): permissive temperature: 2835 ；non permissive temperature: 3640 ts mutant : attenuated mutant ( vaccine mutant )制作减毒活疫苗二 基因重组与重配1. Gene recombination: The exchange of genes between two related viruses which infected the same cell. 2. Reassortment：exchange of genetic material between two segmented viruses which infected the same cell. e.g. Influenza virus:三. Interaction of viral genetic products (non-heritable variation) 1. Complementation (互补作用)：genetic production reactivation between two viruses ( one or both of which may be defective)2. Phenotypic mixing (表型混合): progeny viruses may contain coat components derived from both parents病毒分类Subvirus : refer to the kind of infectious factor which is smaller than virus.1). viroid: - contain RNA only - associated with plant disease. 2). satellite virus : - contain RNA, capsid - need helper virus - associated with plant disease. 3). Prion：infectious protein particales病毒的感染与免疫病毒的致病作用一 病毒感染的传播方式Horizontal transmissionVertical infection：1) rubella virus风疹病毒2) human cytomegalovirus(HCMV)人巨细胞病毒3) herpes simplex virus (HSV) 单纯疱疹病毒4) hepatitis B virus(HBV)乙肝病毒5) human immunodeficiency virus (HIV)人类免疫缺陷病毒二病毒感染的致病机制1. cytocidal effect 杀细胞效应 mainly in naked virus, polioviruscytopathic effecte( CPE)：在体外实验中，通过细胞培养和接种杀细胞性病毒，经一定时间后，可用显微镜观察到细胞变圆、坏死，从瓶壁脱落等现象，称为致细胞病变作用。The presence of the virus often gives rise to morphological changes in the host cell. Any detectable morphological changes in the host cell due to viral infection are known as a cytopathic effect. 2. Steady state infection稳定状态感染 usually caused by enveloped viruses.viruses are produced from the infected cells but the cells are not killed by the process.（1）cell fusion （2）viral Ag expressiononthe infected cell (target cell) membranes 3. Inclusion body 包涵体round or irregular-shaped bodies occurring in the cytoplasm and nuclei of virus-infected cellssuch as：rabies狂犬病, smallpox天花, herpes疱疹, etc.4. Cell apoptosis 细胞凋亡viruses have the potential to initiate or stay the onset of programmed cell death.5. Integration and cell transformation 基因整合与细胞转化integration of the viral genome into cellular DNA .Such as HIV (Retroviruses )；HPV( DNA virus)细胞转化: Infection with oncogenic viruses can cause cell malignant transformation三病毒感染类型Persistent viral infectionViruses exist in the bodies for a long time (6 monthes).1) latent infection潜伏感染: In these infection, the acute disease is follwed by an asymptomatic period during which the virus remains in a latent state. When the patient is exposed to an inciting agent or immunosuppression occurs, reactivation of virus replicaton and disease can occur.Some examples : HSV ,VZV infection2) Chronic infection: 慢性感染 a chronic viral infection tends to develop gradually and last for weeks, months, or even years. virus can be continuously detected. Some examples : hepatitis B, hepatitis C 3) Slow virus infection 慢发病毒感染:Such infections have a prolonged incubation period (years or more than ten years), and a protracted, progressive clinical course. Some examples: AIDS(HIV); SSPE(measles virus) ; prions disease (prions ).抗病毒免疫免疫因素免疫机制巨噬细胞滤过血液中病毒颗粒，使被调理的病毒颗粒灭活，将病毒抗原提呈给T细胞IFN诱导细胞产生抗病毒蛋白，抑制病毒复制，在病毒感染早期其作用NK细胞释放TNF-，TNF-和TNF-，非特异性杀伤病毒感染的靶细胞，早期抗体中和抗体能阻止病毒吸附，有调理作用，主要对细胞外游离的病毒起作用T细胞Th1比Th2重要，CTL能同靶细胞表面的病毒抗原反应，杀伤靶细胞，清除细胞内病毒一 固有免疫Interferon(IFN) anti-virus; anti-tumor ; modify immune responsesMechanisms:IFN combines with specific receptor on cell surface Trigger signal transmission AVP gene actived AVP mRNA transcribed AVP synthesis. AVP mainly consists of two cell-encoded enzymes: 2,5-A synthetase, protein kinase R (PKR); dsRNA2,5-A synthetase 2,5-A activation of Rnase L degrad viral mRNAsinhibit viral protein synthesis inhibition of viral replicationdsRNAPKR activation of PKR phosphorylate eIF-2 ( inactivating eIF-2 ) inhibit viral protein synthesis inhibition of viral replication二适应性免疫Virus neutrilizing antibodies :neutrilizing antibodies - antibodies formed against some surface antigens of the viruses. They can can act on free viruses and neutralize the infectivity of the viruses.Mechanisms: neutr