真核細胞的病毒最新課件

1、真核細胞的病毒最新1Chapter 18The Viruses: Viruses of EucaryotesTEL: ext. 2369N1029李李 景景 欽欽真核細胞的病毒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 display.2011真核細胞的病毒最新2學(xué)習(xí)目標學(xué)習(xí)目標 瞭解病毒感染步

2、驟與複製基本原理 病毒感染型態(tài)與致?。òC轉(zhuǎn)真核細胞的病毒最新3OUTLINE 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 真核細胞的病毒最新4Classification of

3、Animal Viruses Criteriamorphologynucleic acid propertiesgenetic relatedness Including sequencing data and nucleic acid hybridization真核細胞的病毒最新5Double-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 真核細胞的病毒最新6Single-stranded DNA viruses微小病毒科 真核細胞的病毒最新7RNA viruses呼腸孤

4、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 真核細胞的病毒最新8Major vertebrate-infecting viruses真核細胞的病毒最新9Reproduction of Animal Virusesadsorptionpenetration and uncoatingreplication of virus nucleic acidssynthesis and assembly of virionsrelease真核細

5、胞的病毒最新10Adsorption of Virions viral surface proteins and/or enzymes mediate attachment to specific host receptorsreceptor distribution varies lipid rafts microdomains in membranes that involved in virion entrance and assembly 真核細胞的病毒最新11真核細胞的病毒最新12Penetration and Uncoating Two mechanisms used by mos

6、t virusesfusion of envelope with host membraneEndocytosis in some cases only nucleic acid enters host cell真核細胞的病毒最新13Fusion with host membrane真核細胞的病毒最新14Endocytosis enveloped viruscapsid真核細胞的病毒最新15Endocytosis naked virus真核細胞的病毒最新16Replication and Transcription in DNA Viruses early genes encode prote

7、ins involved in take over of host and in synthesis of viral DNA and RNA viral DNA replication usually occurs in early mRNA synthesis usually by host RNA polymerase真核細胞的病毒最新17e.g., parvoviruses ( (微小病毒）微小病毒） single-stranded DNA (ssDNA) viruses small genomes with overlapping genes only encode capsid p

8、roteins use host enzymes for all biosynthetic processes viral DNA only replicated during S period of cell cycleParvovirus B19身軀和四肢出現(xiàn)網(wǎng)狀的紅疹。真核細胞的病毒最新18e.g., herpes simplex virus I (單純泡疹病毒）單純泡疹病毒）uses host RNApolymerase forsynthesis of viralmRNAuses viral DNApolymerase forreplication of genome真核細胞的病毒最新

9、19e.g., poxviruses ( (痘病毒）痘病毒） large, morphologically complex double-stranded DNA (dsDNA) viruses Replication: virion carries that synthesizes early mRNA encodes DNA polymerase and other enzymes needed for DNA replicationPoxviruses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 真核細胞的病毒最新2

10、0e.g., hepadnaviruses ( (肝肝DNADNA病毒）病毒） Transcription: by host RNA polymerase generates several mRNA molecules one is large RNA (pregenome); 3.4 kb Other encode polymerase: (three activity)DNA polymeraseReverse transcriptaseRNase H pregenome converted to dsDNA by virus polymerase Eg. HBV真核細胞的病毒最新21R

11、eplication and Transcription in RNA Viruses very diverse reproductive strategies Four general modes of replication and transcription真核細胞的病毒最新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(zhì)炎的也是屬於這科的polivirus 真核細胞的病毒最新23(呼腸狐病毒）真核細胞的病毒最新24（副黏液病毒-腮腺炎&麻疹;正黏液病毒-感冒)真核細胞的病毒最新25e.g., influenza virus真

12、核細胞的病毒最新26integrates into hostchromosome(勞氏肉瘤病毒）HIV virus真核細胞的病毒最新27Synthesis 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 viru

13、ses site of morphogenesis varies真核細胞的病毒最新28真核細胞的病毒最新29真核細胞的病毒最新30Virion release many viruses use host to aid release process真核細胞的病毒最新31Mechanisms 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

14、 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 真核細胞的病毒最新32Other mechanisms 4. toxicity from high concentrations of viral proteins 5. formation of inclusion bodies can disrupt cell structure 6. chromosomal disr

15、uptions 7 transformation of host cell into malignant cell 真核細胞的病毒最新33Persistent, Latent, and Slow Virus Infections acute infectionsrapid onset and relatively short duration persistent infectionscan last many years真核細胞的病毒最新34Types of persistent infections chronic virus infection clinical symptoms mil

16、d or absent for long periods latent infections virus stops reproducing and remains dormant for some time during latency, symptoms, antivirus-antibodies, and 真核細胞的病毒最新35Possible causes of persistent infections 1. integration of viral genome into host genome 2. decrease in antigenicity of virus 3. mut

17、ation to less virulent and slower reproducing form defective interfering (DI) particle deletion mutant that cannot reproduce and slows reproduction of normal virus真核細胞的病毒最新36Slow virus diseases symptoms take years to emergee.g., subacute sclerosing panencephalitis caused by measles viruse.g., HIV in

18、fections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 真核細胞的病毒最新37Viruses 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(fā)育 reversion to a more primitive or less differentiated state metastasis spread of cancerous cells throughout bo

19、dy真核細胞的病毒最新38腫瘤形成腫瘤形成 (Tumorogenesis/Neoplasia) (Tumorogenesis/Neoplasia) 由於遺傳因素、某些病毒感染、環(huán)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(zhuǎn)（如抑瘤基因tumor suppressor gene及促瘤基因tumor promoter gene)發(fā)生變化造成細胞自然生長或死亡的機制失控，使得，終致於形成一個腫瘤，稱之為腫瘤形成。腫瘤形成可以產(chǎn)生良性腫瘤或是惡性腫瘤。 真核細胞的病毒最新39退行分化退行分化 (Anaplasia) 退行分化是指細胞由分化較好的狀態(tài)退變成一種分化較原始的狀態(tài) 細

20、胞呈現(xiàn)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 真核細胞的病毒最新40Carcinogenesis complex, multistep process often involves oncogenescancer-causing genesmany involved in regulation of cell growth and differentiation some viruses contribute to carcinogenesis真核細胞的病毒最新41Viruses implicated in human cancersE

21、pstein-Barr virusBurkitts lymphomanasopharyngeal carcinomaHepatitis B virusliver cancerHepatitis C virusliver cancerHuman herpesvirus 8Kaposis sarcomahuman papillomaviruscervical cancerHTLV-1 and HTLV-2leukemia真核細胞的病毒最新42Possible mechanisms by which viruses cause cancer 1. carry oncogene into cell a

22、nd 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真核細胞的病毒最新43Plant virusVirion Morphology does not differ significantly from that of animal or bacterial viruses

23、Turnip yellow mosaic virus真核細胞的病毒最新44Plant Virus Taxonomy most are RNA viruses真核細胞的病毒最新45Plant Virus Reproduction e.g., tobacco mosaic virus (TMV)filamentous, plus strand RNA virusRNA replication unclear if catalyzed by host RNA-dependent RNA polymerase or virus encoded enzymeprotein synthesis proce

24、ssed viral genome serves as mRNAnew virions assemble spontaneously真核細胞的病毒最新46Transmission of Plant Viruses 1. by wind, animals, seeds, tubers, and pollen 2. Mechanical damage to plant, due to tough plant cell walls 3. insects真核細胞的病毒最新47Viruses of Fungi and Algae fungal viruseshigher fungi infected w

25、ith dsRNA virusesmost cause latent infectionslower fungi infected by dsRNA or dsDNA virusescause lysis algaedetected in electron micrographs, but not isolated海藻 真核細胞的病毒最新48Insect Viruses Seven virus families Iridoviridae: Reoviridae: cytoplasmic polyhedrosis virus; dsRNA Baculoviridae: Nuclear polyh

26、edrosis virus: inclusion bodies in nucleus Granulosis virus: granular protein inclusion in the cytoplasm formation of granular or Protecting the virions against heat, low pH, and chemicals真核細胞的病毒最新49 have potential as biological control agents for insect pestsHost specificity (invertebrates)Inclusio

27、n bodies better viability in the environmentCommercial production真核細胞的病毒最新50Viroids and Prions viroidsinfectious agents composed only of prionsinfectious agent thought to be composed only of 類病毒 Prion: Proteinaceous infectious particle33-35 kD真核細胞的病毒最新51ViroidsA rodlike shape by intrastrand base pai

28、ring真核細胞的病毒最新52Viroids 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真核細胞的病毒最新53類病毒(Viroids)真核細胞的病毒最新54類病毒類病毒 (Viroids)被感染的蕃被感染的蕃茄茄正常

29、馬鈴薯正常馬鈴薯染病的馬鈴薯染病的馬鈴薯真核細胞的病毒最新55Prions 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 a-helix) in host animal exposure to altered PrP (-sheet) thought to cause disease

30、(proteinase K) Giri et al., PNAS USA , 2006 真核細胞的病毒最新56 Prion是由一種正常的細胞蛋白PrPc 經(jīng)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(jīng)細胞的表面，以glycoinositol phospholipid與細胞膜連結(jié)；對蛋白質(zhì)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(guān)。 經(jīng)過改變的PrPcPrPsc，則具有致病力。相較於PrPc，抵禦蛋白質(zhì)分解脢的能力較強，不易被分解，在病患體內(nèi)可見PrPsc堆積於細胞質(zhì)小泡(cytopla

31、smic vesicles)中。 神經(jīng)元細胞壞死及減少，使大腦皮質(zhì)產(chǎn)生空洞狀退化，大腦組織呈現(xiàn)海綿狀，所以稱海綿樣腦癥 真核細胞的病毒最新57人類普恩蛋白疾病人類普恩蛋白疾病1. 庫雅癥 (CJD)2. 致命性家族失眠癥 (FFI)3. 古魯癥 (Kuru)4. Gerstmann-Straussler-Scheinker 癥(GSS)5. 新變種 CJD 癥 (nvCJD) 真核細胞的病毒最新58普恩蛋白疾病的特徵普恩蛋白疾病的特徵真核細胞的病毒最新59Summary Early viral mRNA and proteins are involved in taking over the

32、host cell and synthesis of viral DNA and RNA. Hepadnaviruses 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 vi

33、rus-associated and newly synthesized transcriptase to make mRNA. 真核細胞的病毒最新60 Retrovirus: Using reverse transcriptase to synthesize a DNA copy of their RNA genome proviral DNA is integrated into the host genome Usually, naked virions are related upon cell lysis. In enveloped virus reproduction, virus

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