真核细胞的病毒30

1、1chapter 18the viruses: viruses of e.tw.twtel: 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 dis

2、play.20112學習目標學習目標 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 4classifica

3、tion of animal viruses criteriamorphologynucleic acid propertiesgenetic relatedness including sequencing data and nucleic acid hybridization5double-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 6single-stranded dna viruses微小病毒科 7rna viruses呼腸孤病毒科 輪狀病毒披蓋病毒科 黃病毒屬

4、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 8major vertebrate-infecting viruses9reproduction of animal virusesadsorptionpenetration and uncoatingreplication of virus nucleic acidssynthesis and assembly of virionsrelease10adsorption of virions viral surface pr

5、oteins and/or enzymes mediate attachment to specific host receptorsreceptor distribution varies lipid rafts microdomains in membranes that involved in virion entrance and assembly 1112penetration and uncoating two mechanisms used by most virusesfusion of envelope with host membraneendocytosis in som

6、e cases only nucleic acid enters host cell13fusion with host membrane14endocytosis enveloped viruscapsid15endocytosis naked virus16replication 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 usuall

7、y occurs in early mrna synthesis usually by host rna polymerase17e.g., parvoviruses ( (微小病毒）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 cyc

8、leparvovirus b19身軀和四肢出現網狀的紅疹。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 genome19e.g., poxviruses ( (痘病毒）痘病毒） large, morphologically complex double-stranded dna (dsdna) viruses replication: virion carries t

9、hat 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 20e.g., hepadnaviruses ( (肝肝dnadna病毒）病毒） transcription: by host rna polymerase generates several mrna molecules one is large rna (pregeno

10、me); 3.4 kb other encode polymerase: (three activity)dna polymerasereverse transcriptasernase h pregenome converted to dsdna by virus polymerase eg. hbv21replication and transcription in rna viruses very diverse reproductive strategies four general modes of replication and transcription22(小rna病毒）pic

11、ornaviruses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&麻疹;正黏液病毒-感冒)25e.g., influenza virus26integrates into hostchromosome(勞氏肉瘤病毒）hiv virus27synthesis and assembly of virus capsids capsid proteins encoded by late genes assembly of naked viruses empty procapsids formed

12、 then nucleic acid inserted assembly of envelope viruses in most cases, similar to assembly of naked viruses site of morphogenesis varies282930virion release many viruses use host to aid release process31mechanisms of host cell damage and cell death 1. inhibition of host dna, rna, and protein synthe

13、sis 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 32other mechanisms 4. toxicity from high concentrations of viral proteins 5. formation of inc

14、lusion bodies can disrupt cell structure 6. chromosomal disruptions 7 transformation of host cell into malignant cell 33persistent, latent, and slow virus infections acute infectionsrapid onset and relatively short duration persistent infectionscan last many years34types of persistent infections chr

15、onic virus infection 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 35possible causes of persistent infections 1. integration of viral genome into host genome 2. decreas

16、e 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 virus36slow virus diseases symptoms take years to emergee.g., subacute sclerosing panencephalitis caused by m

17、easles 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 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退行發育 reversion to a more primitive or less differentiated state metastasis spread of cancerous cell

18、s throughout body38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，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

19、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 40carcinogenesis complex, multistep process often involves oncogenescancer-causing genesmany involved in regulation of cell growth and differentiation some viruses contribute to carcinogenesis41viruses implicated in human cancersepstein-barr virusburk

20、itts lymphomanasopharyngeal carcinomahepatitis b virusliver cancerhepatitis c virusliver cancerhuman herpesvirus 8kaposis sarcomahuman papillomaviruscervical cancerhtlv-1 and htlv-2leukemia42possible mechanisms by which viruses cause cancer 1. carry oncogene into cell and insert it into host genome

21、2. altered cell regulation due to changes in kinase activity or production of regulatory proteins 3. insertion of promoter or enhancer next to cellular oncogene43plant virusvirion morphology does not differ significantly from that of animal or bacterial virusesturnip yellow mosaic virus44plant virus

22、 taxonomy most are rna viruses45plant 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 processed viral genome serves as mrnanew virions assemble spon

23、taneously46transmission of plant viruses 1. by wind, animals, seeds, tubers, and pollen 2. mechanical damage to plant, due to tough plant cell walls 3. insects47viruses of fungi and algae fungal viruseshigher fungi infected with dsrna virusesmost cause latent infectionslower fungi infected by dsrna

24、or dsdna virusescause lysis algaedetected in electron micrographs, but not isolated海藻 48insect viruses seven virus families iridoviridae: reoviridae: cytoplasmic polyhedrosis virus; dsrna baculoviridae: nuclear polyhedrosis virus: inclusion bodies in nucleus granulosis virus: granular protein inclus

25、ion in the cytoplasm formation of granular or protecting the virions against heat, low ph, and chemicals49 have potential as biological control agents for insect pestshost specificity (invertebrates)inclusion bodies better viability in the environmentcommercial production50viroids and prions viroids

26、infectious agents composed only of prionsinfectious agent thought to be composed only of 類病毒 prion: proteinaceous infectious particle33-35 kd51viroidsa rodlike shape by intrastrand base pairing52viroids found in the nucleolus of infected cells do not act as mrna molecules cause disease in plants mec

27、hanism unknown some cause latent infections rna may be replicated by rolling-circle method using host rna polymerase53類病毒(viroids)54類病毒類病毒 (viroids)被感染的蕃被感染的蕃茄茄正常馬鈴薯正常馬鈴薯染病的馬鈴薯染病的馬鈴薯55prions cause degenerative diseases in animals e.g., scrapie bovine spongiform encephalopathy e.g., creutzfeldt-jakob

28、 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(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 pho

29、spholipid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(

30、gss)5. 新變種 cjd 症 (nvcjd) 58普恩蛋白疾病的特徵普恩蛋白疾病的特徵59summary early viral mrna and proteins are involved in taking over the 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

31、virus genome direct synthesis of mrna by a virus-associated transcriptase. double-stranded rna reoviruses use both virus-associated and newly synthesized transcriptase to make mrna. 60 retrovirus: using reverse transcriptase to synthesize a dna copy of their rna genome proviral dna is integrated int

32、o the host genome usually, 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 oncogene virion may insert a promoter next to a cellular oncogene and stimulate the gene to greater activi

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