Intro to Virology - Sept2005

8/14/2019 Intro to Virology - Sept2005

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Introduction to virologyIntroduction to virology

Dr. S JacksonDr. S Jackson

Microbiology DepartmentMicrobiology Department


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ObjectivesObjectives

Introduction The history of virologyIntroduction The history of virology

Classification of virusesClassification of viruses

Basic Properties of virusesBasic Properties of virusesViral ReplicationViral Replication

Viral TransmissionViral Transmission


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The Year 1193 BCThe Year 1193 BCThe PharaohThe Pharaoh SiptahSiptah rules Egypt from 1200-1193 BC whenrules Egypt from 1200-1193 BC when

he dies suddenly at the age of about 20he dies suddenly at the age of about 20..The left leg was withered and the foot was rigidlyThe left leg was withered and the foot was rigidly

expended like a horses hoof- classic paralyticexpended like a horses hoof- classic paralytic

poliomyelitispoliomyelitis


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PoxvirusesPoxviruses

Variola and

Vaccinia


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Smallpox is endemic in China by 1000BC. In response, the practiceSmallpox is endemic in China by 1000BC. In response, the practiceofofvariolationvariolation is developed. Recognizing that survivors of smallpoxis developed. Recognizing that survivors of smallpoxoutbreaks are protected from subsequent infection, variolationoutbreaks are protected from subsequent infection, variolationinvolves inhalation of the dried crusts from smallpox lesions likeinvolves inhalation of the dried crusts from smallpox lesions like

snuff, or in later modifications, inoculation of the pus from a lesionsnuff, or in later modifications, inoculation of the pus from a lesioninto a scratch on the forearm.into a scratch on the forearm.


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On 14th May 1796,On 14th May 1796, EdwardEdwardJennerJennervaccinated an 8 yearvaccinated an 8 yearold boy, James Phipps, withold boy, James Phipps, withmaterial from a cowpox lesionmaterial from a cowpox lesionon the hand of a milkmaid,on the hand of a milkmaid,Sarah Nelmes.Sarah Nelmes.

James, who had never hadJames, who had never hadsmallpoxsmallpox , developed a small, developed a smalllesion at the site of vaccinationlesion at the site of vaccinationwhich healed in 2 weeks.which healed in 2 weeks.On 1st July 1796, JennerOn 1st July 1796, Jennerchallenged the boy bychallenged the boy by

deliberately inoculating himdeliberately inoculating himwith material from a real casewith material from a real caseofofsmallpoxsmallpox !!
http://www.amazon.com/exec/obidos/external-search/?mode=books&keyword=Edward+Jenner&tag=microbiologyimmuhttp://www.amazon.com/exec/obidos/external-search/?mode=books&keyword=Edward+Jenner&tag=microbiologyimmuhttp://www.amazon.com/exec/obidos/external-search/?mode=books&keyword=Edward+Jenner&tag=microbiologyimmuhttp://www.amazon.com/exec/obidos/external-search/?mode=books&keyword=Edward+Jenner&tag=microbiologyimmuhttp://www.amazon.com/exec/obidos/external-search/?mode=books&keyword=smallpox&tag=microbiologyimmuhttp://www.amazon.com/exec/obidos/external-search/?mode=books&keyword=smallpox&tag=microbiologyimmuhttp://www.amazon.com/exec/obidos/external-search/?mode=books&keyword=smallpox&tag=microbiologyimmuhttp://www.amazon.com/exec/obidos/external-search/?mode=books&keyword=smallpox&tag=microbiologyimmuhttp://www.amazon.com/exec/obidos/external-search/?mode=books&keyword=smallpox&tag=microbiologyimmuhttp://www.amazon.com/exec/obidos/external-search/?mode=books&keyword=smallpox&tag=microbiologyimmuhttp://www.amazon.com/exec/obidos/external-search/?mode=books&keyword=Edward+Jenner&tag=microbiologyimmuhttp://www.amazon.com/exec/obidos/external-search/?mode=books&keyword=Edward+Jenner&tag=microbiologyimmu


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"virus" (from the Latin for poison)"virus" (from the Latin for poison)

(1822-1895)(1822-1895) experiments withexperiments withrabiesrabies vaccination.vaccination.

Pasteur does not discriminatePasteur does not discriminatebetween viruses and otherbetween viruses and otherinfectious agents, he originatesinfectious agents, he originatesthe termsthe terms "virus" (from the Latin"virus" (from the Latin

for poison) and "vaccination" (infor poison) and "vaccination" (inhonour of Jennerhonour of Jenner) and develops) and developsthe scientific basis for Jenner'sthe scientific basis for Jenner'sexperimental approach toexperimental approach tovaccination.vaccination.

July 6 1885July 6 1885, Pasteur tests rabies, Pasteur tests rabiestreatment on a human for the firsttreatment on a human for the first

time. Hetime. He vaccinatesvaccinates a child,a child,Joseph Meister, who had beenJoseph Meister, who had beenbitten by a rabid dog, and savesbitten by a rabid dog, and saveshis life.his life.
http://www-micro.msb.le.ac.uk/335/Rhabdoviruses.htmlhttp://www-micro.msb.le.ac.uk/335/Rhabdoviruses.htmlhttp://www-micro.msb.le.ac.uk/335/Rhabdoviruses.html


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Walter Reed (1851-1902)Walter Reed (1851-1902)

During theDuring theSpanish-American WarSpanish-American War&&subsequent building of thesubsequent building of thePanama Canal, AmericanPanama Canal, Americandeaths due to yellow feverdeaths due to yellow feverwere colossal. The diseasewere colossal. The disease

also appeared to be spreadingalso appeared to be spreadingslowly northward into theslowly northward into thecontinental United States.continental United States.

Through experimentalThrough experimentaltransmission to mice, in 1900transmission to mice, in 1900Walter ReedWalter Reed demonstrateddemonstrated

that yellow fever was causedthat yellow fever was causedby a virus, spread byby a virus, spread bymosquitoes.mosquitoes.
http://www.amazon.com/exec/obidos/external-search/?mode=books&keyword=Spanish+American+War&tag=microbiologyimmuhttp://www.amazon.com/exec/obidos/external-search/?mode=books&keyword=Spanish+American+War&tag=microbiologyimmuhttp://www.amazon.com/exec/obidos/external-search/?mode=books&keyword=Spanish+American+War&tag=microbiologyimmu


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The Panama PuzzleThe Panama Puzzle

The name's Reed.The name's Reed.

Walter Reed: Major, US Army Medical Corps.Walter Reed: Major, US Army Medical Corps.

I need your help. It's June 25th, 1900, and I've just beenI need your help. It's June 25th, 1900, and I've just beenposted to Cuba after the end of the Spanish-Americanposted to Cuba after the end of the Spanish-American

war. We lost more men to disease than bullets in thatwar. We lost more men to disease than bullets in thatcampaign. One disease in particular. In Panama, ourcampaign. One disease in particular. In Panama, ourboys have started digging a canal so that our warshipsboys have started digging a canal so that our warshipscan get from the Atlantic to the Pacific. Some canal!can get from the Atlantic to the Pacific. Some canal!We've got big trouble - hundreds of our men have diedWe've got big trouble - hundreds of our men have diedso far from this maddening disease. We call it "yellowso far from this maddening disease. We call it "yellow

jack"jack" (yellow fever)(yellow fever). They get a high fever and jaundice.. They get a high fever and jaundice.Up to half of those who show symptoms die. It's myUp to half of those who show symptoms die. It's myresponsibility to find out what's causing it and put a stopresponsibility to find out what's causing it and put a stopto it. Like I said, I need your help.to it. Like I said, I need your help.


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Global Pandemic -1918Global Pandemic -1918

Influenza AInfluenza A

20 million deaths worldwide20 million deaths worldwide

500,000 deaths in the United States500,000 deaths in the United States..


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DEFINITION:DEFINITION:

Viruses are obligate intracellular parasites.Viruses are obligate intracellular parasites.

Smallest known infective organismSmallest known infective organismUltramicroscopicUltramicroscopic

FilterableFilterable


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Viruses may beViruses may be defineddefined asasacellularacellularorganismsorganismswhosewhose

genomesgenomes consist ofconsist ofnucleic acidnucleic acidobligatelyobligately replicatereplicate inside host cellsinside host cells usingusing hosthost

metabolic machinerymetabolic machinery andand ribosomesribosomes to form ato form a pool ofpool of

componentscomponents which assemble into particles calledwhich assemble into particles called

VIRIONSVIRIONS,, which serve towhich serve to protect the genomeprotect the genome and toand totransfer it to other cellstransfer it to other cells..

They are distinct from other so-calledThey are distinct from other so-called

VIRUS-LIKE AGENTSVIRUS-LIKE AGENTS such as:such as:VIROIDS and PLASMIDS and PRIONSVIROIDS and PLASMIDS and PRIONS
http://www.uct.ac.za/microbiology/tutorial/other_autonomous_or_semi.htmhttp://www.uct.ac.za/microbiology/tutorial/other_autonomous_or_semi.htmhttp://www.uct.ac.za/microbiology/tutorial/other_autonomous_or_semi.htmhttp://www.uct.ac.za/microbiology/tutorial/definitions.htmhttp://www.uct.ac.za/microbiology/tutorial/definitions.htmhttp://www.uct.ac.za/microbiology/tutorial/definitions.htmhttp://www.uct.ac.za/microbiology/tutorial/definitions.htmhttp://www.uct.ac.za/microbiology/tutorial/definitions.htm


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Small size 10-300nmSmall size 10-300nm

(bacteria-1000nm, RBC- 7500nm)(bacteria-1000nm, RBC- 7500nm)

Nucleic acid:Nucleic acid: DNA or RNADNA or RNA

MetabolicallyMetabolically inertinert

No cell wallNo cell wall

Not susceptibleNot susceptible to antibioticsto antibiotics

Do not divide byDo not divide by binary fissionbinary fission like bacterialike bacteria


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A universal system for classifying virusesA universal system for classifying viruses

andand

a unified taxonomya unified taxonomy

has been established by thehas been established by the InternationalInternationalCommittee on Taxonomy of Viruses (ICTV)Committee on Taxonomy of Viruses (ICTV)since 1966.since 1966.

The system makes use of a series of rankedThe system makes use of a series of rankedtaxons, with the:taxons, with the:

OrderOrder((-virales-virales))being the highest currentlybeing the highest currentlyrecognised.recognised.

- then- then FamilyFamily ((-viridae-viridae))-- SubfamilySubfamily ((-virinae-virinae))

-- GenusGenus ((-virus-virus))

-- SpeciesSpecies ( eg: tobacco mosaic virus)( eg: tobacco mosaic virus)


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ClassificationClassification

11 Nucleic acid type (DNA or RNA)Nucleic acid type (DNA or RNA)

22 Size and morphology (symmetry,Size and morphology (symmetry,number of capsomeres, envelope-number of capsomeres, envelope-

33 Susceptibility to physical and chemicalSusceptibility to physical and chemical

agents (ie: ether)agents (ie: ether)44 Presence of specific enzymesPresence of specific enzymes

(Symptomology)(Symptomology)


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PHYSICO-CHEMICAL PROPERTIESPHYSICO-CHEMICAL PROPERTIES

GenomeGenome - DNA or RNA.- DNA or RNA.

NucleocapsidNucleocapsid - proteins- proteinscoating the genomecoating the genome

CapsidCapsid -- outer protein shellouter protein shellEnvelopeEnvelope - lipid outer coat- lipid outer coatderived from the cell in whichderived from the cell in whichthe virus replicates.the virus replicates. NotNotpresent on all virusespresent on all viruses. While. Whilethe lipid membrane is cellthe lipid membrane is cell

coded, viral proteins, usuallycoded, viral proteins, usuallyglycoproteinsglycoproteins are inserted intoare inserted intothe membrane, e.g.the membrane, e.g.hemagglutinin (HA) ofhemagglutinin (HA) ofinfluenza A.influenza A.


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Virus StructureVirus Structure

The function of theThe function of the outer shells (CAPSIDouter shells (CAPSID) of a virus particle is to) of a virus particle is toprotectprotect the fragile nucleic acid genome fromthe fragile nucleic acid genome from

Physical damagePhysical damage --Shearing by mechanical forcesShearing by mechanical forces

Chemical damageChemical damage - UV irradiation (from sunlight) leading to chemical- UV irradiation (from sunlight) leading to chemicalmodification.modification.

Enzyme damageEnzyme damage - Nucleases derived from dead or leaky cells or- Nucleases derived from dead or leaky cells ordeliberately secreted by vertebrates as defence against infection.deliberately secreted by vertebrates as defence against infection.

Protein subunits in a virus capsid are multiply redundant,Protein subunits in a virus capsid are multiply redundant, i.e. present in many copies per particle. Damage to one or more subunitsi.e. present in many copies per particle. Damage to one or more subunits

may render that particular subunit non-functional, but does not destroy themay render that particular subunit non-functional, but does not destroy the

infectivity of the whole particle.infectivity of the whole particle.Virus particles must be assembled utilizing only the informationVirus particles must be assembled utilizing only the informationavailable from theavailable from the capsid + genome)capsid + genome)

Virus particles formVirus particles form regular geometric shapesregular geometric shapes, even though the, even though theproteins from which they are made are irregularly shaped.proteins from which they are made are irregularly shaped.


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can be classified according to

the NUCLEIC ACID present

- either DNA or RNA.


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SOME virionsSOME virions additionally have:additionally have:

ENVELOPESENVELOPES,, ororlipid bilayer MEMBRANESlipid bilayer MEMBRANES::

these always havethese always have viral proteinsviral proteins inserted ininserted inthem (almost alwaysthem (almost always GLYCOPROTEINSGLYCOPROTEINS); these); theseare often referred to asare often referred to as SPIKESSPIKES..

There is usually anThere is usually an inner layerinner layerof proteinof protein MATRIXMATRIX proteinprotein inside the envelope,inside the envelope, usually inusually in

contact with thecontact with the CAPSIDCAPSID protein.protein.


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Human herpesvirusHuman herpesvirus
http://www.uct.ac.za/depts/mmi/stannard/emimages.html


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Formation of Enveloped Virus Particles

Enveloped virus particlesEnveloped virus particlesare formed by buddingare formed by buddingthrough a host cellthrough a host cellmembrane, during whichmembrane, during whichthe particle becomesthe particle becomes

coated with a lipid bilayercoated with a lipid bilayerderived from the cellderived from the cellmembrane. For somemembrane. For someviruses, assembly of theviruses, assembly of thestructure of the particlestructure of the particle

and budding occurand budding occursimultaneously, whereassimultaneously, whereasin others a preformedin others a preformedcore pushes out throughcore pushes out throughthe membrane.the membrane.


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Influenza virusInfluenza virus

Note the helicalNote the helical

structure of the corestructure of the core

seen on the electronseen on the electron

micrographmicrographTheThe hemagglutininhemagglutinin

projectionsprojections assist thisassist this

virus in attachment tovirus in attachment to

the host cellthe host cell


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Effects of physical and chemicalEffects of physical and chemical

agents on virusesagents on virusesHeatHeat

ColdCold

DryingDrying

RediationRediation

Lipid solventsLipid solvents

Antiseptics & disinfectants-formaldehyde, dilute HCL,Antiseptics & disinfectants-formaldehyde, dilute HCL,Sodium hypochloriteSodium hypochlorite

Oxidising agents- chlorine and IodineOxidising agents- chlorine and Iodine

Photodynamic inactivation-Neutral red, Acridine OrangePhotodynamic inactivation-Neutral red, Acridine Orange


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Viruses show 3 types of SymmetryViruses show 3 types of Symmetry

CubicCubic

HelicalHelical

ComplexComplex


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Tobacco mosaic virusTobacco mosaic virus


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Cubic-icosahedralCubic-icosahedral

Ie; AdenovirusIe; Adenovirus


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PoliovirusPoliovirus

Viral particles seen byViral particles seen by

transmission electrontransmission electron

microscopy (TEM) atmicroscopy (TEM) at

a magnification ofa magnification of350,000x)350,000x)

Molecular surface ofMolecular surface of

Poliovirus Type 1Poliovirus Type 1

Mahoney, radiallyMahoney, radially

depth cued, as solveddepth cued, as solvedby X-rayby X-ray

crystallographycrystallography
http://www.bocklabs.wisc.edu/images/polio1.jpghttp://www.pbrc.hawaii.edu/~kunkel/gallery/viruses/page002/24314a.html


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DNA virusesDNA viruses

PoxvirusesPoxviruses

Herpes VirusesHerpes Viruses

AdenovirusesAdenovirusesPapovavirusesPapovaviruses

ParvoviursesParvoviurses

HepadnavirusesHepadnaviruses


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AdenovirusesAdenoviruses

are non-envelopedare non-enveloped

icosahedral particles.icosahedral particles.

The capsid is built upThe capsid is built up

from 252 capsomersfrom 252 capsomers

((TT=25), of which 240 are=25), of which 240 arehexavalent and 12hexavalent and 12

(situated at the apices)(situated at the apices)

are pentavalent.are pentavalent.

AA "penton fibre""penton fibre"projectsprojectsfrom each apex.from each apex.
http://www.uct.ac.za/depts/mmi/stannard/adeno.html


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Examples of RNA VirusesExamples of RNA Viruses

OrthomyxovirusOrthomyxovirus

ParamyxovirusParamyxovirus

RhabdovirusRhabdovirus

TogavirusTogavirus

FlavivirusFlavivirus

BunyavirusBunyavirus

ReovirusReovirus

PicornavirusPicornavirus

CoronavirusCoronavirus

CalicivurusCalicivurus

RetrovirusRetrovirus

ArenavirusArenavirus


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Viruses enter the body of the host

in a variety of ways, for example...


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PathogenesisPathogenesis

Host defense-Host defense- Non-specific interferonNon-specific interferon

production by infected cellsproduction by infected cells

Specific immunity-Specific immunity- by production of viralby production of viral

antibody (IgG, IgM, IgA)antibody (IgG, IgM, IgA)

Call mediated immunity-Call mediated immunity-

T-lymphocytesT-lymphocytes


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Viral replicationViral replication

Absorption or AttachmentAbsorption or Attachment

PenetrationPenetration

UncoatingUncoating

TranscriptionTranscriptionTranslationTranslation

TranscriptionTranscription

TranslationTranslation

AssemblyAssembly

ReleaseRelease


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Generalized Scheme for Virus Replication


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Absorption or AttachmentAbsorption or Attachment

The virus particle absorbsThe virus particle absorbsto the cell surface at ato the cell surface at a

receptor sitereceptor siteEach host cell >500,000Each host cell >500,000receptorsreceptors


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PenetrationPenetration

The cell membraneThe cell membrane

invaginates aroundinvaginates around

the adsorbed virusthe adsorbed virus

particleparticlevacoulevacoule


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UncoatingUncoating

Protein coat (capsid) isProtein coat (capsid) is

removed by the hostremoved by the host

enzymesenzymes

Eclipse PhaseEclipse Phase (( viral nucleic acidviral nucleic acid

indistuingishable fromindistuingishable from

host cell nucleic acid)host cell nucleic acid)


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Early mesenger RNA (mRNA)Early mesenger RNA (mRNA)


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Late mRNA from progeny DNALate mRNA from progeny DNA


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TranslationTranslation

Late mRNA codes for structural proteinsLate mRNA codes for structural proteins


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AssemblyAssemblymaturation of new virusmaturation of new virus

particlesparticles

ReleaseRelease- of new viruses from host cell- of new viruses from host cell


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BacteriophageBacteriophage

B t i h


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BacteriophageBacteriophageAA virus which infects bacteriavirus which infects bacteria..

SensorsSensors on the ends of its 'legs' recognize bindingon the ends of its 'legs' recognize bindingsites on the surface of the host's cell, and thissites on the surface of the host's cell, and thistriggers the bacteriophage into actiontriggers the bacteriophage into action

The bacteriophage binds to the surface of the host,The bacteriophage binds to the surface of the host,punctures the cell with its injection tube, and thenpunctures the cell with its injection tube, and theninjects its own genetic blueprint.injects its own genetic blueprint.

This genetic information subverts the host cell'sThis genetic information subverts the host cell'snormal operation and sets the cell's biosyntheticnormal operation and sets the cell's biosyntheticmachinery to work creating replicas of the virus.machinery to work creating replicas of the virus.

These newly created viruses escape from the cellThese newly created viruses escape from the celland then float about dormant until one happens toand then float about dormant until one happens tocome into contact with a new host cell.come into contact with a new host cell.


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ViroidsViroids are small (200-400nt), circular RNAare small (200-400nt), circular RNAmolecules with a rod-like secondary structuremolecules with a rod-like secondary structurewhich possess no capsid or envelopewhich possess no capsid or envelope

VirusoidsVirusoids are satellite, viroid-like molecules,are satellite, viroid-like molecules,somewhat larger than viroids (e.g. approximatelysomewhat larger than viroids (e.g. approximately1000nt)1000nt)

PrionsPrions are infectious agents believed to consistare infectious agents believed to consistof a single type of protein molecule with noof a single type of protein molecule with nonucleic acid component.nucleic acid component.

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Intro to Virology - Sept2005

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