Virology病毒學(xué)第一課件網(wǎng)網(wǎng)站2021/01/211Introduction1.Thediscoveryofvirus2.Featureandconceptionofvirus3.Relationshipbetweenvirusesanddiseasesofhumanbeing1892年發(fā)現(xiàn)第一個(gè)病毒---煙草花葉病毒2021/01/2122.FeatureandconceptionofvirusFeatureConceptionThemostimportantdifferencebetweenvirusesandothermicrobes?

RNAorDNA?modeofmultiplication---

selfreplication

體積微小結(jié)構(gòu)簡(jiǎn)單嚴(yán)格寄生復(fù)制增殖

DNAorRNAnon-celluraltypemultiplyonlyinlivingandsusceptiblecells2021/01/2133.Relationshipbetweenvirusesanddiseasesofhumanbeing2021/01/214BasicProperties病毒的基本性狀(6版p22~31)2021/01/215OutlineSizeandShapeofVirusesStructureandChemicalCompositionMultiplicationofVirusesEffectofphysicochemicalagentsonvirusClassificationofVirusesViralHeredity&Variation(p81~83)(6版p22~31,81~83)2021/01/216300×250nm

葡萄球菌

煙草花葉病毒立克次體450nm衣原體390nm15×300nm65×95nm70nm

腺病毒30nm

脊灰病毒40nm

乙腦病毒100nm流感病毒10nm卵白蛋白

噬菌體1000nm

痘苗病毒Ⅰ.SizeandShapeofViruses

Measuringunit

(nanometer,nm)?d=30~300nm?visibleonlywith

EM1.SizeofvirusDivideinto3types---small,medianand

largevirus

(絕大數(shù)＜150nm)2.Shapeofviruses2021/01/217﹤病毒的形態(tài)與大小球形桿狀子彈狀磚塊狀蝌蚪狀2.Shapeofviruses中型病毒＜50nm50~200nm200~300nm2021/01/2181.Structureofvirionnucleicacidpeplomer(spike)capsidnucleocapsidcapsomere(Nakedvirus)envelopeviralcoreEnvelopedvirus成熟的、有感染性的、完整的病毒顆粒Ⅱ.StructureandChemicalComposition2021/01/219

Viralcore---viralnucleicacid⑴

Onlyonetypeofnucleicacid?

eitherDNAorRNA?

diversity*doubleorsinglestranded(ds-/ss-)

*circularorlinear,inonepieceorsegmented

*plusandminusstrand⑵Viralgenome(DNAorRNA)

---determineinfectivity,replication,heredityandvariationofvirus（DNA病毒大多數(shù)為雙鏈，RNA病毒多數(shù)為單鏈）2021/01/2110

Proteincoat----capsid(衣殼)⑴Consistsofrepeatingpolypeptidesubunitscalledcapsomere(殼粒)

⑵Symmetryinarrangement→threesymmetricarchitecture⑶

Function

?protect?participateinviralinfection?antigenicityHelicalsymmetryCubicsymmetryComplexsymmetryStructureofthesimplestvirion:Nucleicacid+capsid=Nucleocapsid?五鄰體六鄰體(決定病毒的親嗜性,介導(dǎo)病毒進(jìn)入宿主細(xì)胞)(核衣殼)2021/01/2111

Envelopeandspike

?

Envelopedvirus

?

Compositionofenvelope

?

Peplomerorspike

?

Function(virion

nucleocapsid+envelope)(胞膜子粒刺突)2021/01/2112

capsid核酸刺突

衣殼

包膜病毒體的結(jié)構(gòu)

核衣殼DNA/RNA核衣殼裸病毒包膜病毒

(裸病毒)

病毒體(包膜病毒)衣殼核酸（DNA/RNA）包膜2021/01/21132.Chemicalcomposition

ofviruses

Nucleicacid

Protein

lipidandcarbohydrate⑴

structuralprotein

⑵

non-structuralprotein

(capsid,matrixandenvelope)2021/01/2114病毒的復(fù)制周期生物合成1.MultiplicationofvirusModeofmultiplication

---self-replication

Replicativecycle⑴adsorption/attachment↓⑵penetration↓⑶uncoating

→⑷biosynthesis

↓⑸assembly&releaseⅢ.MultiplicationofVirus2021/01/2115⑴Adsorptionorattachment

?Nonspecificadsorption?Specificcombination

---virionadsorbtospecificreceptoronthesurfaceofsusceptiblecells

---staticelectricity-combinationbetweenvirusandcell(decidetissueorcell-tropism,suchasgp120ofHIV---CD4molecule)2021/01/2116

⑶Uncoating---Theviralnucleiacidisreleasedfromthecapsid⑵Penetration?nakedvirus---byendocytosisorviropexis

?envelopedvirus---byfusionofviralenvelopewithhost-cellmembrane(病毒胞膜與宿主細(xì)胞膜融合)(吞飲或胞飲)2021/01/2117

⑷Biosynthesis?

include:

replicationofnucleicacidandproteinsynthesis

?

biosyntheticsite*DNAinthenucleus,RNAinthecytoplasm*proteininthecytoplasm

earlyprotein(functionprotein)lateprotein(structuralprotein)(eclipseperiod,隱蔽期)2021/01/2118Biosynthesisofds-DNAvirusparentalds-DNAearlymRNAearlyproteininthecytoplasmprogenyds-DNAinnucleus

latermRNAlaterproteininthecytoplasm

半保留復(fù)制

利用核內(nèi)依賴DNA的RNA多聚酶轉(zhuǎn)錄⑴biosynthesisofearlyprotein---依賴DNA的DNA聚合酶等⑵replicationofprogenyDNA⑶biosynthesisoflateprotein

⑴⑵⑶DNA聚合酶2021/01/2119Biosynthesisofss-RNAvirusparental㈩ss-RNAearlyproteininthecytoplasmactsdirectlyasmRNA㈠ss-RNA(±RNA)laterproteinprogeny

㈩ss-RNA

(復(fù)制中間型)

----RNAmustfirsttranscribethecomplementaryplusstrand*㈠ss-RNAvirus(依賴RNA的RNA聚合酶)+RNAactsasmRNA2021/01/2120

⑸Assembly&release

?assemblyandmaturation

?release

*nakedvirus*envelopedvirusassembly:DNAvirus---inthenucleusRNAvirus---inthecytoplasm2021/01/2121Replicationcycleofvirusadsorptionbiosynthesis

assemblyandrelease

uncoatingproteinandnucleicacidpenetration?

progenyviruses

?

producecelleffects---damageandlysisofcells2021/01/21222.Abnormalmultiplicationofviral&interference

Abortiveinfection

(頓挫感染)

non-permissivecells&permissivecells(容納性細(xì)胞)Interference

Defectivevirus

兩種病毒同時(shí)感染同一種細(xì)胞,發(fā)生一種病毒抑制另一種病毒復(fù)制的現(xiàn)象稱為干擾現(xiàn)象

指缺陷病毒與其完整病毒(非缺損病毒)同時(shí)感染同一細(xì)胞時(shí),能干擾完整病毒的增殖,發(fā)揮干擾作用的缺陷病毒為缺陷干擾顆粒(DIP)defectiveinterferingparticle(DIP)2021/01/2123

紫外線、χ線和射線可滅活

耐抗生素和甘油消毒劑可滅活；包膜病毒對(duì)脂溶劑敏感

Ⅳ.Effectofphysicochemicalagentsonvirus耐冷不耐熱pH5.0以下或pH9.0以上迅速滅活2021/01/21241.Basisofclassification

Type&structureofnucleicacid

Structureofvirus

(envelope,symmetry)

Sizeandshapeofvirus

SensitivetolipidsolventⅤ.Classificationofvirusesp302021/01/21252.Categoriesofviruses

DNAvirusesRNAvirusesDNAandRNAretroviruses(嗜肝DNA病毒科、逆轉(zhuǎn)錄病毒科)Subvirus2021/01/2126

比病毒更小的傳染因子稱為亞病毒Subvirus---pathogenicagentsofunconventionalvirus

(非尋常病毒）⑴Viroids(類病毒)?ss-RNA,possessnocapsidorenvelope?

causeplantdisease⑵satellites(衛(wèi)星病毒)→→plantdisease

⑶prion(朊粒)---新型感染因子?canencodeself-capsidprotein?

satellitesRNAmolecules(曾經(jīng)稱為擬病毒)(ssRNA;capsidproteinfromhelpervirus)2021/01/2127⑶Prion(朊粒)/Virino(朊病毒)①possessnostructureofvirionandcontainnodetectablenucleicacidinprions

②consistofprionprotein(PrP,朊蛋白)?specificproteinwithinfectivity

故稱為傳染性蛋白粒子,即prion,又稱為朊蛋白(PrP)?encodedbygeneofnormalhostcellsandnohomologywithnormalprotein③resistanttophysicalandchemicalagents④2isomerofPrP?PrPc

(cellularprionprotein)?PrPsc(scrapieprionprotein)difference?(highly)(p335)2021/01/2128

sensitivetoproteinaseKresistanttoproteinaseK

PrPC

↓PrPSC(具有致病性和傳染性)⑤Diseasesasso-ciatedwithprions

?humandisease?commoncharacteristics(Kurudisease,CJD,vCJD,etc.)---afataldiseaseofCNS

大量PrPSC聚合和沉積→神經(jīng)細(xì)胞空泡變性→海綿狀腦病(主要臨床表現(xiàn):癡呆、共濟(jì)失調(diào)、震顫等)傳染性癡呆病2021/01/2129Ⅵ.ViralHeredityandVariation1.Twoimportantvariations

Variationsinantigenicity

Variationsinvirulence3.Recombination

&reassortment

4.Geneintegration5.Phenotypevariation

p812.Genemutation第一課件網(wǎng)網(wǎng)站2021/01/21302.Mutation

Conceptionofmutantandvariant

Importantmutant---temperaturesensitivemutant(tsmutant)ts突變株通常是減毒株且保留免疫原性，可用于制備減毒活疫苗在容許性溫度(28~35℃)下可增殖,而在非容許性溫度(37~40℃)條件下不能增殖的病毒株稱為ts突變株突變株變異株2021/01/2131

3.Generecombination

andreassortment

Generecombination

(重組)

Reassortment

(重配)

(segmentedgenome)(nonsegmentedgenome)++4.Geneintegration5.Phenotypevariation

2021/01/2132病毒的感染與免疫

InfectionandImmunityofViruses2021/01/2133PathogenesisofVirusesModesofViralTransmission

TypesofViralInfectionAntiviralImmunityOutlinep48~53p62~652021/01/2134Ⅰ.PathogenesisofVirus1.DirecteffectsofviralinfectiononhostcellsCytolyticinfection

(溶細(xì)胞型感染)?Infectionofnakedviruses→cytocidaleffect

?Mechanismofcelldeathandlysis*病毒一次大量釋放→細(xì)胞裂解死亡*細(xì)胞生物合成被抑制→細(xì)胞病變死亡*衣殼蛋白的直接殺傷作用或自溶?Invitroinfectionofcytocidalvirus→cytopathiceffect(CPE,致細(xì)胞病變作用)2021/01/2135Steady-stateinfection

*fusionofcells→formmultinucleatedgiantcells

*appearanceofnewantigenonthesurfaceofhostcells

?

Infectionofenvelopedviruses

?

Changeofcellmembrane(穩(wěn)定狀態(tài)感染)(細(xì)胞融合形成多核巨細(xì)胞)2021/01/2136GeneIntegration&celltransformation(基因整合與細(xì)胞轉(zhuǎn)化）(Relationshipbetweenvirusesandcancers)

Inclusionbodyformation

(包涵體形成)Cellapoptosis（細(xì)胞凋亡）包涵體存在的位置、染色性有助于鑒別2021/01/2137

3.Immunesuppression(suppressionofimmunefunction)2.Immunopathogenesis

ImmunopathogenesismediatedbyAbImmunopathogenesismediatedbycellsImmunopathogenesisofautoimmunityofviralinfection(TypeⅡ,Ⅲhypersensitivity)(typeⅣhypersensitivity)(LSP→IR;commonAg→crossreaction)2021/01/2138

Ⅱ.Modesof

ViralTransmission1.horizontaltransmission

2.verticaltransmission

conception

portalofentry

conception

portalofentry?skin

?

mucousmembrane?

viablood?

placenta?

vagina(包括產(chǎn)后經(jīng)乳汁傳給嬰兒)(orperinataltransmission,圍產(chǎn)期傳播)垂直傳播的危害!

人群不同個(gè)體間的傳播方式稱為水平傳播,由此引起的感染為水平感染病毒通過(guò)胎盤(pán)或產(chǎn)道,從親代直接傳給子代的方式為垂直傳播,由此引起的感染為垂直感染注意:*皮膚、消化道核呼吸道為病毒的三大入侵門(mén)戶!*杜絕醫(yī)源性傳播!

2021/01/2139Ⅲ.TypesofViralInfectionvirusportalofentryInfectionordisease

1.Inapparentviralinfection

2.ApparentviralinfectionspreadtohosttargetorganIR(不表現(xiàn)癥狀,可獲免疫力或成為病毒攜帶者;重要傳染源)

Acuteviralinfection

Persistentviralinfection(持續(xù)性感染)?也稱病原消滅型感染?局部或全身有明顯臨床癥狀?

病毒持續(xù)存在

?有癥狀/無(wú)癥狀而長(zhǎng)期帶毒

?重要傳染源2021/01/2140

chronicinfection病毒持續(xù)存在血液或組織中,經(jīng)?；蜷g歇排毒,病程長(zhǎng)如HBV

latentinfection

病毒長(zhǎng)期潛伏組織而不排毒;激活后急性發(fā)作期才可檢出病毒;可反復(fù)發(fā)作如HSV、VZV所致感染slowvirusinfection潛伏期很長(zhǎng),CNS的致死性感染,病情呈亞急性進(jìn)行性加重→死亡.如麻疹病毒→亞急性硬化性全腦炎(SSPE)

Persistentviralinfection

潛伏期很長(zhǎng),癥狀一出現(xiàn)呈進(jìn)行性加重→死亡如HIV→AIDSdelayedcomplicationafteracuteviralinfection2021/01/21411.NonspecificimmunityBarriersEffectsofcellsAntibacterialsubstancesinnormaltissuesandbodyfluide

(placentabarrier)(M,

NKcell)(similartoantibacterialimmunity)(IFN)Ⅳ.AntiviralImmunity(p62~65)2021/01/2142

PrincipalleukocytesfibroblastslymphocytescellsourceNKcellIFNinducersdsRNAdsRNAmitogensvirusvirusorantigenAntiviralinfection+++++Anti-tumor++++Immunoregulation++++PropertyIFN-IFN-IFN-Interferon

(IFN)⑴

definition干擾素是由病毒或其他干擾素誘生劑刺激機(jī)體多種細(xì)胞所產(chǎn)生的一種具有抗病毒、抗腫瘤和免疫調(diào)節(jié)等多種生物學(xué)活性的糖蛋白⑵typesandproperties2021/01/2143bindstosurfacereceptorofanneighbouringcells⑶

Mechanismofantiviralactivitythesynthesisofantiviralprotein(AVP)induceIFNbyblockingthetranslationofviralproteinsinhibitthereplicationofvirusesAVP:⑴2’-5’Asynthetase(2’-5’A合成酶)⑵proteinkinase(蛋白激酶)⑶phosphodiesterase(磷酸二脂酶)→降解病毒mRNA→滅活蛋白合成的啟動(dòng)因子→抑制病毒蛋白翻譯2021/01/2144

⑷Featureofantiviralactivity

?inhibitreplicationofavarietyofviruses---broadspectrum?indirecteffect?species-specific(廣譜抗病毒活性,即抗病毒作用是非特異的)

(不直接殺滅病毒)(有種屬特異性)2021/01/2145⑸ActionofIFNinantiviralimmunity----inhibitreplicationofvirusthebody’sfirst-linedefenseagainstviralinfection?discontinueviralinfection?limitthespreadofvirusandprotectneighbouringcells

IFN干擾素產(chǎn)生早于特異性免疫

specificimmunity2021/01/2146

NKcell⑴Killingvirus-infectedcells(naturalkilleractivity)⑵Mechanismofkillingtargetcell?

AMofNKcellbindingtocorrespondingligandoftargetcell→necrosisorapoptosisofcells?

mediateADCC?

releasekillermadiator病毒感染細(xì)胞病毒感染細(xì)胞2021/01/21472.SpecificimmunityHumoralimmunity

?virus-neutralizingantibodies?non-neutralizingantibodyViralprotein(processingandpresenting)induceHI/CMI清除胞外游離病毒*neutralizeinfectivityofvirus*types(IgG/IgM/sIgA)andmechanism阻止吸附與穿入易感細(xì)胞*hemagglutinationinhibitionAb→inhibithemagglutination*complementfixationAb→opsonization2021/01/2148Cell-mediatedimmunity

?DirectkillingactivityofCTL?AntiviraleffectofCD4+Th1cell

*釋放IFN-及TNF激活M和NK細(xì)胞*促進(jìn)CTL增殖等

*具有病毒特異性*分泌IFN-、TNF發(fā)揮抗病毒作用

清除細(xì)胞內(nèi)病毒,終止病毒感染2021/01/21493.LastedtimeofimmunityTransientimmunity

Long-lastingimmunity

(orlifelongimmunity)

（短暫免疫）（持久免疫或牢固免疫）2021/01/21506版

p112Detection,Preventionand病毒感染的檢查方法2021/01/2151Ⅰ.DiagnosisofViralInfection

1.Collectionandtransportofspecimens2.Isolationandidentifi-cationofviruses3.Serologicaldiagnosisofviralinfection4.Quickdiagnosisp112~1162021/01/21521.Collectionandtransport

ofspecimens(principlesofcollectingspecimens)

Specimensofviralisolationordetectionofviralnucleicacid

Specimensofserologicaltests(intime,properspecimensandpropertreatment)?

Double-specimensofserum

?

asinglesampleofserum2021/01/2153?animalinoculation?embryonatedeggsinoculation?tissueorcellculture(typesofcells---原代細(xì)胞;二倍體細(xì)胞;傳代細(xì)胞)(sitesofinoculation)(susceptibleanimal,properroute)

Principlesofviralculture

Threemainmethods---multiplyonlyinlivingandsusceptiblecells2.Isolationandidentificationofviruses2021/01/2154

Isolationofvirusspecimen(removingbacteria)

inoculatepreliminarydiagnosis(intothesusceptiblehostassoonaspossible)animalinoculationembryonatedeggcellcultureserologicidentification

已知抗體鑒定未知抗原(病