真核细胞的病毒-2.ppt

1,Chapter 18,The Viruses: Viruses of Eucaryotes,.tw .tw TEL: ext. 2369 N1029,Department of Biotechnology Kaohsiung Medical University,李 景 欽,真核細胞的病毒,Fundamentals of microbiology, first edition, 2005 L.M. Prescott, J.P. Harley and D.A. Klein. Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.,2011,2,學習目標,瞭解病毒感染步驟與複製基本原理 病毒感染型態與致病（癌）機轉,3,OUTLINE,The process of virus infection Viral replication and transcription DNA and RNA virus Mechanism of host cell damage and cell death Type of viral infection Viruses and cancer Plant, Fungi, Algae and insect viruses Virions and prions,4,Classification of Animal Viruses,Criteria morphology nucleic acid properties genetic relatedness Including sequencing data and nucleic acid hybridization,5,Double-stranded DNA viruses,單純皰疹病毒,皰疹病毒,水痘帶狀皰疹病毒,EB病毒,痘病毒,天花,桿狀病毒科,乳多瘤病毒科,人類乳頭瘤狀病毒,腺病毒科,虹彩病毒,6,Single-stranded DNA viruses,微小病毒科,7,RNA viruses,呼腸孤病毒科,輪狀病毒,披蓋病毒科,黃病毒屬,肝炎病毒屬(Hepacivirus)：C型肝炎病毒(Hepatitis C virus),冠狀病毒科,微小病毒,正黏液病毒科,本雅病毒科,沙狀病毒科,彈狀病毒科,狂犬病,8,Major vertebrate-infecting viruses,9,Reproduction of Animal Viruses,adsorption penetration and uncoating replication of virus nucleic acids synthesis and assembly of virions release,10,Adsorption of Virions,viral surface proteins and/or enzymes mediate attachment to specific host receptors receptor distribution varies lipid rafts microdomains in membranes that involved in virion entrance and assembly,11,12,Penetration and Uncoating,Two mechanisms used by most viruses fusion of envelope with host membrane Endocytosis in some cases only nucleic acid enters host cell,13,Fusion with host membrane,14,Endocytosis enveloped virus,capsid,15,Endocytosis naked virus,16,Replication and Transcription in DNA Viruses,early genes encode proteins involved in take over of host and in synthesis of viral DNA and RNA viral DNA replication usually occurs in nucleus early mRNA synthesis usually by host RNA polymerase,17,e.g., parvoviruses (微小病毒）,single-stranded DNA (ssDNA) viruses small genomes with overlapping genes only encode capsid proteins use host enzymes for all biosynthetic processes viral DNA only replicated during S period of cell cycle,Parvovirus B19,身軀和四肢出現 網狀的紅疹。,18,e.g., herpes simplex virus I (單純泡疹病毒）,uses host RNA polymerase for synthesis of viral mRNA,uses viral DNA polymerase for replication of genome,19,e.g., poxviruses (痘病毒）,large, morphologically complex double-stranded DNA (dsDNA) viruses Replication: Cytoplasm virion carries DNA-dependent RNA polymerase that synthesizes early mRNA encodes DNA polymerase and other enzymes needed for DNA replication,Poxviruses中的Variola virus造成天花(smallpox)，其中vaccinia virus是用來製造天花疫苗的病毒,20,e.g., hepadnaviruses (肝DNA病毒）,circular, dsDNA genome Transcription: by host RNA polymerase generates several mRNA molecules one is large RNA (pregenome); 3.4 kb Other encode polymerase: (three activity) DNA polymerase Reverse transcriptase RNase H pregenome converted to dsDNA by virus polymerase (Reverase transcriptase) Eg. HBV,21,Replication and Transcription in RNA Viruses,very diverse reproductive strategies Four general modes of replication and transcription,22,(小RNA病毒）,Picornaviruses中的Enterovirus即是所謂的腸病毒，其中造成脊隨灰白質炎的也是屬於這科的polivirus,23,(呼腸狐病毒）,24,（副黏液病毒-腮腺炎 正黏液病毒-感冒),25,e.g., influenza virus,26,integrates into host chromosome,(勞氏肉瘤病毒）,HIV virus,27,Synthesis and Assembly of Virus Capsids,capsid proteins encoded by late genes assembly of naked viruses empty procapsids formed then nucleic acid inserted assembly of envelope viruses in most cases, similar to assembly of naked viruses site of morphogenesis varies,28,29,30,Virion release,many viruses use host actin filaments to aid release process,31,Mechanisms of host cell damage and cell death,1. inhibition of host DNA, RNA, and protein synthesis 2. lysosome damage causes release of hydrolytic enzymes into cell 3. alteration of plasma membrane can lead to attack of host cell by immune system, eg SARS can lead to cell fusion, forming syncytium,多核體,32,Other mechanisms,4. toxicity from high concentrations of viral proteins 5. formation of inclusion bodies can disrupt cell structure 6. chromosomal disruptions 7 transformation of host cell into malignant cell,33,Persistent, Latent, and Slow Virus Infections,acute infections rapid onset and relatively short duration persistent infections can last many years,34,Types of persistent infections,chronic virus infection virus almost always detectable clinical symptoms mild or absent for long periods latent infections virus stops reproducing and remains dormant for some time during latency, symptoms, antivirus-antibodies, and viruses are not detectable,35,Possible causes of persistent infections,1. integration of viral genome into host genome 2. decrease in antigenicity of virus 3. mutation to less virulent and slower reproducing form defective interfering (DI) particle deletion mutant that cannot reproduce and slows reproduction of normal virus,36,Slow virus diseases,symptoms take years to emerge e.g., subacute sclerosing panencephalitis caused by measles virus e.g., HIV infections,麻疹,亞急性硬化泛腦炎為感染麻疹病毒所造成的慢性腦炎,37,Viruses and Cancer,tumor growth or lump of tissue Neoplasia贅瘤形成 abnormal new cell growth and reproduction due to loss of regulation Anaplasia退行發育 reversion to a more primitive or less differentiated state metastasis spread of cancerous cells throughout body,38,腫瘤形成 (Tumorogenesis/Neoplasia),由於遺傳因素、某些病毒感染、環境的刺激如輻射線、紫外線等引起染色體中控制腫瘤生長或死亡的基因及機轉（如抑瘤基因tumor suppressor gene及促瘤基因tumor promoter gene)發生變化造成細胞自然生長或死亡的機制失控，使得細胞不斷的增值或永不凋亡，終致於形成一個腫瘤，稱之為腫瘤形成。腫瘤形成可以產生良性腫瘤或是惡性腫瘤。,39,退行分化 (Anaplasia),退行分化是指細胞由分化較好的狀態退變成一種分化較原始的狀態 細胞呈現比較原始，甚至接近胚胎時期的不成熟細胞 依照退行分化的程度不同，會失去部分或是全部原來細胞的功能,40,Carcinogenesis,complex, multistep process often involves oncogenes cancer-causing genes many involved in regulation of cell growth and differentiation some viruses contribute to carcinogenesis,41,Viruses implicated in human cancers,42,Possible mechanisms by which viruses cause cancer,1. carry oncogene into cell and insert it into host genome 2. altered cell regulation due to changes in kinase activity or production of regulatory proteins 3. insertion of promoter or enhancer next to cellular oncogene,43,Plant virus Virion Morphology,does not differ significantly from that of animal or bacterial viruses,Turnip yellow mosaic virus,44,Plant Virus Taxonomy,most are RNA viruses,45,Plant Virus Reproduction,e.g., tobacco mosaic virus (TMV) filamentous, plus strand RNA virus RNA replication unclear if catalyzed by host RNA-dependent RNA polymerase or virus encoded enzyme protein synthesis processed viral genome serves as mRNA new virions assemble spontaneously,46,Transmission of Plant Viruses,1. by wind, animals, seeds, tubers, and pollen 2. Mechanical damage to plant, due to tough plant cell walls 3. insects,47,Viruses of Fungi and Algae,fungal viruses higher fungi infected with dsRNA viruses most cause latent infections lower fungi infected by dsRNA or dsDNA viruses cause lysis algae detected in electron micrographs, but not isolated,海藻,48,Insect Viruses,Seven virus families Iridoviridae: Reoviridae: cytoplasmic polyhedrosis virus; dsRNA Baculoviridae: Nuclear polyhedrosis virus: inclusion bodies in nucleus Granulosis virus: granular protein inclusion in the cytoplasm formation of granular or polyhedral inclusion bodies Protecting the virions against heat, low pH, and chemicals,49,have potential as biological control agents for insect pests Host specificity (invertebrates) Inclusion bodies better viability in the environment Commercial production,50,Viroids and Prions,viroids infectious agents composed only of circular ssRNA prions infectious agent thought to be composed only of protein,類病毒,Prion: Proteinaceous infectious particle,33-35 kD,51,Viroids,A rodlike shape by intrastrand base pairing,52,Viroids,Found in the nucleolus of infected cells do not act as mRNA molecules cause disease in plants mechanism unknown some cause latent infections RNA may be replicated by rolling-circle method using host RNA polymerase,53,類病毒(Viroids),單股環狀的 RNA 分子, 無蛋白質外殼, 核酸基因也不製造任何蛋白質 2. 1961年首先自馬鈴薯紡錘狀疾病塊莖中發現 3. 1971年由 T.O. Diener 命名為類病毒 (Viroids) 4. 分子大小約為 300400 個核甘酸, 為一般病毒的數千分之一 5. 只發現於植物, 於植物細胞核內複製, 造成植物疾病 6. 致病原因不明, 可能係干擾素主 mRNA 的形成,54,類病毒 (Viroids),被感染的蕃茄,正常馬鈴薯,染病的馬鈴薯,55,Prions,cause degenerative diseases in animals e.g., scrapie bovine spongiform encephalopathy e.g., Creutzfeldt-Jakob disease(人類庫茲德-賈克氏病) PrP (prion protein) is present in “normal” form (a-helix) in host animal exposure to altered PrP (-sheet) thought to cause disease,(proteinase K),Giri et al., PNAS USA , 2006,56,Prion是由一種正常的細胞蛋白PrPc 經過改變而得。 製造PrPc的基因僅含單一的exon，且在正常細胞中僅含一個PrPc基因 PrPc主要位於神經細胞的表面，以glycoinositol phospholipid與細胞膜連結；對蛋白質水解脢(Protease)有高度敏感性；推測其生理作用與突觸(synapse)的功能相關。 經過改變的PrPcPrPsc，則具有致病力。相較於PrPc，抵禦蛋白質分解脢的能力較強，不易被分解，在病患體內可見PrPsc堆積於細胞質小泡(cytoplasmic vesicles)中。 神經元細胞壞死及減少，使大腦皮質產生空洞狀退化，大腦組織呈現海綿狀，所以稱海綿樣腦症,57,人類普恩蛋白疾病,1. 庫雅症 (CJD) 2. 致命性家族失眠症 (FFI) 3. 古魯症 (Kuru) 4. Gerstmann-Straussler-Scheinker 症(GSS) 5. 新變種 CJD 症 (nvCJD),58,