《真核细胞的病毒.ppt》由会员分享，可在线阅读，更多相关《真核细胞的病毒.ppt（62页珍藏版）》请在三一办公上搜索。
1、1,Chapter 18,The Viruses:Viruses of Eucaryotes,TEL:ext.2369N1029,Department of BiotechnologyKaohsiung Medical University,李 景 欽,真核細胞的病毒,Fundamentals of microbiology,first edition,2005L.M.Prescott,J.P.Harley and D.A.Klein.Copyright The McGraw-Hill Companies,Inc.Permission required for reproduction or
2、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 infectionViral replication and transcriptionDNA and RNA virusMechanism of host cell damage and cell deathType of viral infectionViruses and cancerPlant,Fungi,Algae and insect virusesVirions and prions,4,Classification
3、of Animal Viruses,Criteriamorphologynucleic acid propertiesgenetic relatednessIncluding 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
4、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,adsorptionpenetration and uncoatingreplication of virus nucleic acidssynthesis and assembly of virionsrelease,10,Adsorption of Virions,viral s
5、urface proteins and/or enzymes mediate attachment to specific host receptorsreceptor distribution varieslipid rafts microdomains in membranes that involved in virion entrance and assembly,11,12,Penetration and Uncoating,Two mechanisms used by most virusesfusion of envelope with host membraneEndocyto
6、sisin 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 genesencode proteins involved in take over of host and in synthesis of viral DNA and RNAviral DNA re
7、plication usually occurs in nucleusearly mRNA synthesisusually by host RNA polymerase,17,e.g.,parvoviruses(微小病毒）,single-stranded DNA(ssDNA)virusessmall genomes with overlapping genesonly encode capsid proteinsuse host enzymes for all biosynthetic processesviral DNA only replicated during S period of
8、 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 RNApolymerase forsynthesis of viralmRNA,uses viral DNApolymerase forreplication of genome,19,e.g.,poxviruses(痘病毒）,large,morphologically complex double-stranded DNA(dsDNA)virusesReplication:Cytoplasmvirion carri
9、es DNA-dependent RNA polymerase that synthesizes early mRNAencodes 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 genomeTranscription:by host RNA polymerasegenerates severa
10、l mRNA moleculesone is large RNA(pregenome);3.4 kbOther encode polymerase:(three activity)DNA polymeraseReverse transcriptaseRNase Hpregenome converted to dsDNA by virus polymerase(Reverase transcriptase)Eg.HBV,21,Replication and Transcription in RNA Viruses,very diverse reproductive strategiesFour
11、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 hostchromosome,(勞氏肉瘤病毒）,HIV virus,27,Synthesis and Assembly of Virus Capsids,capsid proteinsencoded
12、by late genesassembly of naked virusesempty procapsids formed then nucleic acid insertedassembly of envelope virusesin most cases,similar to assembly of naked virusessite of morphogenesis varies,28,29,30,Virion release,many viruses use host actin filaments to aid release process,31,Mechanisms of hos
13、t cell damage and cell death,1.inhibition of host DNA,RNA,and protein synthesis2.lysosome damagecauses release of hydrolytic enzymes into cell3.alteration of plasma membranecan lead to attack of host cell by immune system,eg SARScan lead to cell fusion,forming syncytium,多核體,32,Other mechanisms,4.tox
14、icity from high concentrations of viral proteins5.formation of inclusion bodiescan disrupt cell structure6.chromosomal disruptions7 transformation of host cell into malignant cell,33,Persistent,Latent,and Slow Virus Infections,acute infectionsrapid onset and relatively short durationpersistent infec
15、tionscan last many years,34,Types of persistent infections,chronic virus infectionvirus almost always detectableclinical symptoms mild or absent for long periodslatent infectionsvirus stops reproducing and remains dormant for some timeduring latency,symptoms,antivirus-antibodies,and viruses are not
16、detectable,35,Possible causes of persistent infections,1.integration of viral genome into host genome2.decrease in antigenicity of virus3.mutation to less virulent and slower reproducing formdefective interfering(DI)particle deletion mutant that cannot reproduce and slows reproduction of normal viru
17、s,36,Slow virus diseases,symptoms take years to emergee.g.,subacute sclerosing panencephalitis caused by measles viruse.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,tumorgrowth or lump of tissueNeoplasia贅瘤形成 abnormal new cell growth and reproduction due to loss of regulationAna
18、plasia退行發育 reversion to a more primitive or less differentiated statemetastasisspread 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
19、，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 processoften involves oncogenescancer-causing genesmany involved in regulation of cell growth and differentiationsome viruses contrib
20、ute 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 genome2.altered cell regulation due to changes in kinase activity or production of regulatory proteins3.insertion of promoter or enhanc
21、er next to cellular oncogene,43,Plant virusVirion 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 virusRNA r
22、eplicationunclear if catalyzed by host RNA-dependent RNA polymerase or virus encoded enzymeprotein synthesisprocessed viral genome serves as mRNAnew virions assemble spontaneously,46,Transmission of Plant Viruses,1.by wind,animals,seeds,tubers,and pollen2.Mechanical damage to plant,due to tough plan
23、t cell walls3.insects,47,Viruses of Fungi and Algae,fungal viruseshigher fungiinfected with dsRNA virusesmost cause latent infectionslower fungiinfected by dsRNA or dsDNA virusescause lysisalgaedetected in electron micrographs,but not isolated,海藻,48,Insect Viruses,Seven virus familiesIridoviridae:Re
24、oviridae:cytoplasmic polyhedrosis virus;dsRNABaculoviridae:Nuclear polyhedrosis virus:inclusion bodies in nucleusGranulosis virus:granular protein inclusion in the cytoplasmformation of granular or polyhedral inclusion bodiesProtecting the virions against heat,low pH,and chemicals,49,have potential
25、as biological control agents for insect pestsHost specificity(invertebrates)Inclusion bodies better viability in the environmentCommercial production,50,Viroids and Prions,viroidsinfectious agents composed only of circular ssRNAprionsinfectious agent thought to be composed only of protein,類病毒,Prion:
26、Proteinaceous infectious particle,33-35 kD,51,Viroids,A rodlike shape by intrastrand base pairing,52,Viroids,Found in the nucleolus of infected cellsdo not act as mRNA moleculescause disease in plantsmechanism unknownsome cause latent infectionsRNA may be replicated by rolling-circle method using ho
27、st 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 animalse.g.,scr
28、apiebovine spongiform encephalopathye.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 animalexposure 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
29、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.Gerstm
30、ann-Straussler-Scheinker 症(GSS)5.新變種 CJD 症(nvCJD),58,普恩蛋白疾病的特徵,潛伏期長(約 110 年)從感染部位經淋巴系統,侵入中樞神經,血液與肌肉中尚未發現病原蛋白尚無有效的實驗室檢驗方法從症狀上判斷:腦組織萎縮,產生空洞(顯微鏡下呈海綿狀)產生痴呆症狀肌肉喪失協調能力吞嚥困難發病後約一年死亡,59,Summary,Early viral mRNA and proteins are involved in taking over the host cell and synthesis of viral DNA and RNA.Hepadnav
31、iruses use reverase transcriptase to replicate dsDNA genome.The genome of positive ssRNA can act as an mRNA.The negative ssRNA virus genome direct synthesis of mRNA by a virus-associated transcriptase.Double-stranded RNA reoviruses use both virus-associated and newly synthesized transcriptase to mak
32、e mRNA.,60,Retrovirus:Using reverse transcriptase to synthesize a DNA copy of their RNA genomeproviral DNA is integrated into the host genomeUsually,naked virions are related upon cell lysis.In enveloped virus reproduction,virus release and envelop formation Virus and cancer:Virus bring a cancer-causing gene or oncogeneVirion may insert a promoter next to a cellular oncogene and stimulate the gene to greater activity,61,The End,62,
