virology-201119022601 (1).pdf

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1. INTRODUCTION TO VIROLOGY

2. Background/Discovery
TheconceptbehindmodernvirologycanbetracedbacktoAdolf
Mayer,DimitriIvanofskyandMartinusBeijerinckwho,
independentlyinthelate1880’s,discoveredwhatwaslatertobe
calledtobaccomosaicvirus(TMV).
Theirdiscoveriesledtothedescriptionsoffilterableagents,too
smalltobeseenwiththelightmicroscope,thatcouldbegrownin
livingcellsandcausedisease.
Thefirstfilterableagentfromanimals,footandmouthdisease
virus,wasdescribedbyLoefflerandFroschin1898andthefirst
humanfilterableagentdiscoveredwasyellowfevervirus,discovered
byWalterReedin1901.
Theterm‘virus’derivesfromtheLatinforslimyliquidorpoison
andwasgraduallyintroducedduringthisperiodtoreplacetheterm
‘filterableagents’.

3. •Thefirstvirustobevisualizedbyx-raycrystallographyandelectron
microscopywasTMV,reportedin1941and1939,respectively.
•Theseadvancesintroducedthenotionthatviruseswerestructurally
composedofrepeatingsubunits.
•
•FrederickTwortandFelixd’Herelle,workingindependently,are
creditedwiththediscoveryofviruseswhichcouldinfectandlyse
bacteriain1915.
•D’Herelleintroducedtheterm‘bacteriophages’fortheseagentsand
alsodescribedtheconceptsofvirusadsorptiontoitstarget,celllysis
andreleaseofinfectiousparticles.
•Overthenext35-40years,workwithphagesledtonumerous
discoveriesincludinghowtheintroductionofDNAintoatargetcell
couldreproduceitselfandtheregulationofcellularmacromolecular
synthesisdirectedbyviruses.
•Inessence,thefieldofmolecularbiologywasopenedupduring
thisperiod.

4. •Advancesinanimalvirologywerenotedthroughoutthe
20thcenturybutthemajorbreakthroughcamethrough
thedevelopmentoftissueculturesystemsthatled,for
example,totheisolationofpoliovirusbyEndersetal.in
1949.
•Thismarkedlyfacilitateddetailedstudyofthisagentand,
mostimportantly,thedevelopmentofpoliovirusvaccines.
•Theensuing50yearshaveseendiagnosticvirology
matureasafieldwiththediscoveryofnewagentsand
diseasesandtheparalleldeterminationoftheimportance
ofvirusesinourunderstandingofmolecularbiologyand
cancer.

5. A.Aswithotherinfectiousagentswhichcausehumandisease,the
outcomeoftheinteractionofaparticularviruswiththehumanhostis
dependentonbothpathogenandhostfactors.Viralstrainswithina
genusmayhavedifferentialcelltropisms,replicationcapacitiesand
cytopathogeniceffects.Asanexample,strainsofHIVmaypreferentially
targetmonocyte/macrophagesorT-lymphocytes,mayusedifferentco-
receptors(e.g.,thechemokinereceptors,CCR5orCXCR4)onthecell
surface,mayreplicatetodifferentlevelsandmayinducedifferent
degreesofcellkilling.ThesetraitshavedirectclinicalcorrelatesforHIV
infectedpersonswithrespecttotheratesofCD4celldeclineand
progressiontoclinicalAIDS.Onthehostside,thenatureofthe
exposureandthehostimmunestatusareprobablythetwomost
importantdeterminantsofoutcome.
Thus,thekeyelementsofthevirushostinteractionare:
1.Viralstrain.
2.Inoculumsize.
3.Routeofexposure.
4.Susceptibilityofhost(i.e.,istherepre-existentimmunityfrompast
exposureorvaccination?).
5.Immunestatusandageofhost.

6. Definitions
A.Virus particle or virion.
An infectious agent composed of nucleic acid (RNA or DNA), a protein
shell (capsid) and, in some cases, a lipid envelope.
Virionshave full capacity for replication when a susceptible target cell is
encountered.
1.Capsid and capsomeres. The protein coat that surrounds the viral
nuclei acid. This is composed of repeating protein 2 subunits called
capsomeres.
Generally, capsidshave either helical or icosahedralsymmetry.
2. Nucleocapsid. The complete protein-nucleic acid complex.
B. Satellite or Defective Viruses.
Viruses which require a second virus (helper virus) for replication.
Hepatitis delta virus is the major humanpathogenexample.
It requires the presence of hepatitis B virus to complete its replication
cycle.

7. OR
Virus"poisonoussubstance,"fromLatinvirus"poison
Avirusisachainofnucleicacids(DNAorRNA)whichlivesin
ahostcell,usespartsofthecellularmachinerytoreproduce,and
releasesthereplicatednucleicacidchainstoinfectmorecells.
Avirusisoftenhousedinaproteincoatorproteinenvelope,a
protectivecoveringwhichallowsthevirustosurvivebetweenhosts.

8. Terminology:
Virion= virus particle
Capsid= protein shellwhich surrounds and protects the genome. It is built up of
multiple (identical) protein sub-units calledcapsomers.Capsidsare
eithericosahedralortubularin shape
Nucleocapsid= genome plus capsid
Envelope =lipid membrane which surrounds some viruses. It is derived from the
plasma membrane of the host cell
Peplomers=proteins found in the envelope of the virion. They are usually
glycosylatedand are thus more commonly known asglycoproteins
Viroids. Viroidsare the smallest known autonomously replicating molecules. They
consist of single-stranded, circular RNA, 240-375 residues in length and are plant
pathogens.
D. Prions. Prionsare not viruses but are often discussed within this microbiologic category.
Prionsare infectious protein molecules that contain no definable nucleic acid and are
responsible for the transmissible and familial spongiform encephalopathies: The
pathogenic prionprotein, PrPSc, is formed from a normal human protein, PrPC, through
post-translational processing.

9. VirusStructure
Aviruscantakeonavarietyofdifferentstructures.
Thesmallestvirusisonly17nanometers,barelylongerthanan
averagesizedprotein.
Thelargestvirusisnearlyathousandtimesthatsize,at1,500
nanometers.
Thisisreallysmall.Ahumanhairisapproximately20,000
nanometersacross.
Thismeansthatmostvirusparticlesarewellbeyondthecapability
ofanormallightmicroscope.Belowisascanningelectron
microscope(SEM)imageoftheEbolavirus.
Theexactstructureofavirusisdependentupon
whichspeciesservesasitshost.
Aviruswhichreplicatesinmammaliancellswillhaveaproteincoat
whichenablesittoattachtoandinfiltratemammaliancells.
Theshape,structure,andfunctionoftheseproteinschanges
dependingonthespeciesofvirus.Atypicalviruscanbeseenbelow.

10. Viral Tegument

11. Theabovevirusshowsthetypicalstructureavirustakes,aviralgenome
surroundedbyashieldofproteins.
Thevariousenvelopeproteinswillenablethevirustointeractwiththehostcell
itfinds.Partoftheproteincoatwillthenopen,puncturethroughthecell
membrane,anddeposittheviralgenomewithinthecell.
Theproteincoatcanthenbediscarded,astheviralgenomewillnowreplicate
withinthehostcell.
Thereplicatedvirusmoleculeswillbepackagedwithintheirownproteincoats,
andbereleasedintotheenvironmenttofindanotherhost.
Whilemanyvirusparticlestakeasimpleshapeliketheoneabove,someare
muchmorecomplicated.

12. III. Classification
Viral classification has been confusing and oft-changing over the
years. In the past, viruses were often classified by host, target organ
or vector and these are still used vernacularly (e.g., the hepatitis
viruses).
Modern classification is based on the following three characteristics:
A.Type of viral nucleic acid (RNA or DNA, single-stranded or
double stranded) and its replication strategy.
B.Capsidsymmetry (icosahedralor helical).
C.Presence or absence of lipid envelope.

14. Theaboveimageshowsaphage,atypeofviruswhichspecializes
onbacterialcells.
Theproteincoatofaphageismuchmorecomplex,andhasa
varietyofspecializedparts.
Theheadportioncontainstheviralgenome.
Thecollar,sheath,baseplate,andtailfibersarepartofan
intricatesystemtoattachtoandinjectthegenomeintoa
bacterialcell.
Thetailfibersgraspthebacterialcell,pullingthebaseplateupto
thecellwallormembrane.
Thesheathandcollarcompress,puncturethecell,anddeposit
theDNAintothebacterialcell.

15. Size
Virusesareusuallymuchsmallerthanbacteriawiththevast
majoritybeingsubmicroscopic.
Whilemostvirusesrangeinsizefrom5to300nanometers(nm),
inrecentyearsanumberofgiantviruses,includingMimiviruses
andPandoraviruseswithadiameterof0.4micrometers(µm),
havebeenidentified.
Foracomparisonofthesizeofavirus,abacterium,andahuman
cell,scrolldowntohowbigis...ontheCellSizeandScale
ResourceattheUniversityofUtahwebpage
(seeFigure1A,Figure1B,andFigure1C),

16. Figure 1A: Sizes and Shapes of Viruses (Animal RNA Viruses

17. Figure 1B: Sizes and Shapes of Viruses (Animal DNA Viruses)

18. Figure 1C: Sizes and Shapes of Viruses (Bacteriophages)

19. Figure 2: Viral Structure (Helical Virus). (B) Viral Structure (Polyhedral Virus), (C) Viral
Structure (Enveloped Helical Virus), D: Viral Structure (Enveloped Polyhedral Virus), (F)
Viral Structure (Binal) Illustration of a T-even bacteriophageconsisting of a head,
sheath, and tail.

20. IsaVirusLiving?
Thisisacomplicatedquestion.Acellisconsideredtobeliving
becauseitcontainsallthenecessarycomponentstoreplicateits
DNA,grow,anddivideintonewcells.Thisistheprocessalllife
takes,whereitisasingle-celledorganismoramulti-cellular
organism.Somepeopledonotconsideraviruslivingbecauseavirus
doesnotcontainallofthemechanismsnecessarytoreplicateitself.
Theywouldsaythatavirus,withoutahostcell,cannotreplicateon
itsownandisthereforenotalive.
Yet,bythedefinitionoflifelaidoutbefore,itseemsthatwhena
virusisinsideofahostcellitdoeshaveallthemachineryitneedsto
survive.Theproteincoatitexistsinoutsideofacellistheequivalent
ofabacterialspore,asmallcapsulebacteriaformaroundthemselves
tosurviveharshconditions.Scientistswhosupportavirusbeinga
livingorganismsnotethesimilaritybetweenavirusinaproteincoat
andabacterialspore.Neitherorganismisactivewithintheir
protectivecoat,theyonlybecomeactivewhentheyreachfavorable
conditions.

21. Virus Classification

22. Classificationofvirus
1.OntheBasisofGeneticMaterialPresent
2.Onthebasisofthepresenceofanumberofstrands
3.OntheBasisofPresenceofEnvelope
4.VirusClassificationbyCapsidStructure
5.OntheBasisofShapesoftheViruses
6.ClassificationofVirusontheBasisofStructure
7.OntheBasisoftheTypeofHost
8.ClassificationofVirusontheBasisofModeof
Transmission
9.ClassificationofVirusontheBasisofReplication
PropertiesandSiteofReplication
10.BaltimoreClassification

23. Classificationofvirus
Virusesaresmallobligateintracellularparasites,whichbydefinitioncontain
eitheraRNAorDNAgenomesurroundedbyaprotective,virus-codedprotein
coat.
Virusesrangefromthestructurallysimpleandsmallparvovirusesand
picornavirusestothelargeandcomplexpoxvirusesandherpesviruses.
Virusesareclassifiedonthebasisofmorphology,chemicalcomposition,and
modeofreplication.
Thevirusesthatinfecthumansarecurrentlygroupedinto21families,
reflectingonlyasmallpartofthespectrumofthemultitudeofdifferent
viruseswhosehostrangesextendfromvertebratestoprotozoaandfromplants
andfungitobacteria.

24. 1.OntheBasisofGeneticMaterialPresent
Virusesaresmall,nonlivingparasites,whichcannotreplicate
outsideofahostcell.
Avirusconsistsofgeneticinformation—eitherDNAorRNA—
coatedbyaprotein.
Accordingly,theyareclassifiedasDNAvirusesandRNAviruses.
Thenucleicacidmaybesingleordoublestranded,circularor
linear,segmentedorunsegmented

25. DNAviruses
Astheirnameimplies,DNAvirusesuseDNAastheirgeneticmaterial.
SomecommonexamplesofDNAvirusesareparvovirus,papillomavirus,and
herpesvirus.
DNAvirusescanaffectbothhumansandanimalsandcanrangefromcausing
benignsymptomstoposingveryserioushealth.
RNAviruses
ThevirusthatpossessesRNAasgeneticmaterialarecalledRNAviruses.
Rotavirus,poliovirus,yellowfevervirus,denguevirus,hepatitisC
virus,measlesvirus,rabiesvirus,influenzavirusandEbolavirusareexamples
ofRNAvirus.
DNA-RNAviruses
TheRNAtumorvirusescalledLeukovirusesandRous’svirusesunusually
containbothDNAandRNAasgeneticmaterial

26. 2.Onthebasisofthepresenceofanumberofstrands
Double-strandedDNA
Itisfoundinpoxviruses,thebacteriophagesT2,T4,T6,T3,
T7andLamda,herpesviruses,adenovirusesetc.
Single-strandedDNA
Itisfoundinbacteriophagesφ,X,74bacteriophages.
Double-strandedRNA
Ithasbeenfoundwithinviralcapsidinthereovirusesofanimals
andinthewoundtumourvirusandricedwarfvirusesofplants.
Single-strandedRNA
ItisfoundinmostoftheRNAviruseseg:tobaccomosaicvirus,
influenzavirus,poliomyelitis,bacteriophageMS-2,Avianleukemia
virus.

27. 3.OntheBasisofPresenceofEnvelope
Theenvelopeisalipid-containingmembranethatsurroundssome
virusparticles.Itisacquiredduringviralmaturationbyabudding
processthroughacellularmembrane
Virusencodedglycoproteinsareexposedonthesurfaceofthe
envelope.Theseprojectionsarecalledpeplomers.
EnvelopedVirus
DNAviruses:Herpesviruses,Poxviruses,Hepadnaviruses
RNAviruses:Flavivirus,Togavirus,Coronavirus,HepatitisD,
Orthomyxovirus,Paramyxovirus,Rhabdovirus,Bunyavirus,
Filovirus
Retroviruses
Non-EnvelopedVirus
DNAviruses-parvovirus,adenovirusandpapovavirus.
RNAviruses-Picornavirus,HepatitisAvirusandHepatitisEvirus.

28. 4.VirusClassificationbyCapsidStructure
1.Nakedicosahedral:HepatitisAvirus,polioviruses
2.Envelopedicosahedral:Epstein-Barrvirus,herpessimplex
virus,rubellavirus,yellowfevervirus,HIV-1
3.Envelopedhelical:Influenzaviruses,mumpsvirus,measles
virus,rabiesvirus
4.Nakedhelical:Tobaccomosaicvirus
5.Complexwithmanyproteins:somehavecombinationsof
icosahedralandhelicalcapsidstructures.Herpesviruses,
smallpoxvirus,hepatitisBvirus,T4bacteriophage.

30. 5.OntheBasisofShapesoftheViruses
Mostoftheanimalvirusesareroughlysphericalwithsome
exceptions.
1.Rabiesvirus:Bulletshaped
2.Ebolavirus:Filamentousshaped
3.Poxvirus:Brickshaped
4.Adenovirus:Spacevehicleshaped

31. 6.ClassificationofVirusontheBasisofStructure
Cubicalvirus:Theyarealsoknownasicosahedralsymmetryvirus
Eg.Reovirus,Picornavirus.
Spiralvirus:Theyarealsoknownashelicalsymmetryvirus
Eg.Paramyxovirus,orthomyxovirus.
Radialsymmetryvirus:eg.Bacteriophage.
Complexvirus:eg.Poxvirus

32. 7.OntheBasisoftheTypeofHost
Theviruscanbeclassifiedonthebasisofthetypeofhost.
Theyare:
1.Animalviruses
2.Plantviruses
3.Bacteriophage

33. AnimalViruses
Theviruseswhichinfectandliveinsidetheanimalcellincluding
manarecalledanimalviruses.
Eg;influenzavirus,rabiesvirus,mumpsvirus,poliovirusetc.
TheirgeneticmaterialisRNAorDNA.
PlantViruses
•Thevirusesthatinfectplantsarecalledplantviruses.Their
geneticmaterialisRNAwhichremainsenclosedintheprotein
coat.
•Someplantvirusesaretobaccomosaicvirus,potatovirus,beet
yellowvirusandturnipyellowvirusetc.
Bacteriophages
Viruseswhichinfectbacterialcellsareknownasbacteriophageor
bacteriaeaters.
TheycontainDNAasgeneticmaterial.Therearemanyvarieties
ofbacteriophages.
Usually,eachkindofbacteriophagewillattackonlyonespeciesor
onlyonestrainofbacteria.

34. 8.ClassificationofVirusontheBasisofModeofTransmission
Virustransmittedthroughrespiratoryroute:
Eg,Swineflu,Rhinovirus
Virustransmittedthroughfaeco-oralroute:
Eg.HepatitisAvirus,Poliovirus,Rotavirus
Virustransmittedthroughsexualcontacts:
Eg.Retrovirus
Virustransmittedthroughbloodtransfusion:
Eg.HepatitisBvirus,HIV
Zoonoticvirus:
Virustransmittedthroughbitingofinfectedanimals;
Eg.Rabiesvirus,Alphavirus,Flavivirus

35. 9.ClassificationofVirusontheBasisofReplicationProperties
andSiteofReplication
Replicationandassemblyincytoplasmofhost:
AllRNAvirusreplicateandassembleincytoplasmofhostcell
exceptInfluenzavirus
Replicationinnucleusandassemblyincytoplasmofhost:
Influenzavirus,Poxvirus
Replicationandassemblyinnucleusofhost:
AllDNAvirusesreplicateandassembleinnucleusofhostcellexcept
Poxvirus.
VirusreplicationthroughdsDNAintermediate:
AllDNAvirus,RetrovirusandsometumorcausingRNA
virusreplicatesthroughdsDNAasintermediates.
VirusreplicationthroughssRNAintermediate:
AllRNAvirusexceptReovirusandtumorcausingRNAviruses.

36. 10.BaltimoreClassification
Themostcommonlyusedsystemofvirusclassification
wasdevelopedbyNobelPrize-winningbiologistDavid
Baltimoreintheearly1970s.
Inadditiontothedifferencesinmorphologyand
geneticsmentionedabove,theBaltimoreclassification
schemegroupsvirusesaccordingtohowthemRNAis
producedduringthereplicativecycleofthevirus.

40. GroupI
virusescontaindouble-strandedDNA(dsDNA)astheirgenome.
TheirmRNAisproducedbytranscriptioninmuchthesameway
aswithcellularDNA.
GroupII
viruseshavesingle-strandedDNA(ssDNA)astheirgenome.They
converttheirsingle-strandedgenomesintoadsDNAintermediate
beforetranscriptiontomRNAcanoccur.
GroupIII
virusesusedsRNAastheirgenome.Thestrandsseparate,andone
ofthemisusedasatemplateforthegenerationofmRNAusing
theRNA-dependentRNApolymeraseencodedbythevirus.

41. Group IV
This group viruses have ssRNAas their genome with a positive
polarity.Positive polaritymeans that the genomic RNA can serve
directly as mRNA.
Intermediates of dsRNA, calledreplicative intermediates, are
made in the process of copying the genomic RNA.
Multiple, full-length RNA strands of negative polarity
(complementary to the positive-stranded genomic RNA) are
formed from these intermediates, which may then serve as
templates for the production of RNA with positive polarity,
including both full-length genomic RNA and shorter viral
mRNAs.

42. Group V
viruses contain ssRNAgenomes with anegative polarity,
meaning that their sequence is complementary to the mRNA. As
with Group IV viruses, dsRNAintermediates are used to make
copies of the genome and produce mRNA.
In this case, the negative-stranded genome can be converted
directly to mRNA.
Additionally, full-length positive RNA strands are made to serve
as templates for the production of the negative-stranded
genome.

43. GroupVI
viruseshavediploid(twocopies)ssRNAgenomesthatmustbe
converted,usingtheenzymereversetranscriptase,todsDNA;the
dsDNAisthentransportedtothenucleusofthehostcelland
insertedintothehostgenome.
Then,mRNAcanbeproducedbytranscriptionoftheviralDNA
thatwasintegratedintothehostgenome.
GroupVII
viruseshavepartialdsDNAgenomesandmakessRNA
intermediatesthatactasmRNA,butarealsoconvertedbackinto
dsDNAgenomesbyreversetranscriptase,necessaryforgenome
replication.

44. THANK YOU