Microbiology: A Microbiology: A Systems Approach, 2Systems Approach, 2ndnd

ed.ed.Chapter 6: An Introduction to the Chapter 6: An Introduction to the

VirusesViruses

6.1 The Search for the Elusive 6.1 The Search for the Elusive VirusVirus

Viruses were too small to be seen with the first Viruses were too small to be seen with the first microscopesmicroscopes

The cause of viral infections was unknown for yearsThe cause of viral infections was unknown for years Louis Pasteur first proposed the term Louis Pasteur first proposed the term virusvirus 1890s1890s

Ivanovski and Beijerinck showed that a disease in Ivanovski and Beijerinck showed that a disease in tobacco was caused by a virustobacco was caused by a virus

Loeffler and Frosch discovered an animal virus that Loeffler and Frosch discovered an animal virus that causes foot –and-mouth disease in cattlecauses foot –and-mouth disease in cattle

Many years of experimentation showed what we Many years of experimentation showed what we know today and by the 1950s virology had grownknow today and by the 1950s virology had grown

6.2 The Position of Viruses in the 6.2 The Position of Viruses in the Biological SpectrumBiological Spectrum

Can infect every type of cellCan infect every type of cell Cannot exist independently from the host cell, so Cannot exist independently from the host cell, so

aren’t considered living thingsaren’t considered living things However, since they can direct life processes they However, since they can direct life processes they

are often considered more than lifeless moleculesare often considered more than lifeless molecules Referred to as infectious particles, either active or Referred to as infectious particles, either active or

inactiveinactive Obligate intracellular parasitesObligate intracellular parasites Cannot multiply unless they invade a specific host Cannot multiply unless they invade a specific host

cell and instruct its genetic and metabolic cell and instruct its genetic and metabolic machinery to make and release new virusesmachinery to make and release new viruses

6.3 The General Structure of 6.3 The General Structure of VirusesViruses

Figure 6.1

Size RangeSize Range Smallest infectious agentsSmallest infectious agents Most are so small, they can only be seen with an Most are so small, they can only be seen with an

electron microscopeelectron microscope Animal virusesAnimal viruses

Proviruses- around 20 nm in diameterProviruses- around 20 nm in diameter Mimiviruses- up to 450 nm in lengthMimiviruses- up to 450 nm in length

Viewing virusesViewing viruses Special stains and an electron microscopeSpecial stains and an electron microscope Negative staining outlines the shapeNegative staining outlines the shape Positive staining shows internal detailsPositive staining shows internal details Shadowcasting techniqueShadowcasting technique

Figure 6.2

Viral Components: Capsids, Viral Components: Capsids, Nucleic Acids, and EnvelopesNucleic Acids, and Envelopes

Molecular structure- composed of regular, Molecular structure- composed of regular, repeating subunits that give rise to their crystalline repeating subunits that give rise to their crystalline appearanceappearance

Contain only those parts needed to invade and Contain only those parts needed to invade and control a host cellcontrol a host cell External coatingExternal coating

• CapsidCapsid• Envelope- in 13 of the 20 families of animal virusesEnvelope- in 13 of the 20 families of animal viruses• If no envelope, called naked virusIf no envelope, called naked virus

Core Core • DNADNA• RNARNA

The capsid and the nucleic acid together are called the The capsid and the nucleic acid together are called the nucleocapsidnucleocapsid

Fully formed virus that is able to establish an Fully formed virus that is able to establish an infection in a host cell- infection in a host cell- virionvirion

Figure 6.4

The Viral Capsid: The Protective The Viral Capsid: The Protective Outer ShellOuter Shell

Constructed from identical subunits called Constructed from identical subunits called capsomerscapsomers

Made up of protein moleculesMade up of protein molecules Two different typesTwo different types

HelicalHelical• Rod-shaped Rod-shaped capsomerscapsomers• Assemble in to helical nucleocapsidAssemble in to helical nucleocapsid

Figure 6.5

Figure 6.6

IcosahderalIcosahderal Three-dimensional, 20-sided figure with 12 Three-dimensional, 20-sided figure with 12

evenly spaced cornersevenly spaced corners Although they all display this symmetry, there Although they all display this symmetry, there

are wide variationsare wide variations

Figure 6.7

Figure 6.8

Figure 6.9

Figure 6.10

The Viral EnvelopeThe Viral Envelope

Enveloped virusesEnveloped viruses take a bit of the host take a bit of the host cell membrane in the form of an envelopecell membrane in the form of an envelope

In the envelope, some or all of the regular In the envelope, some or all of the regular membrane proteins are replaced with viral membrane proteins are replaced with viral proteinsproteins

Some proteins form a binding layer Some proteins form a binding layer between the envelope and the capsidbetween the envelope and the capsid

Glycoproteins remain exposed as Glycoproteins remain exposed as spikesspikes (peplomers)- essential for attachment(peplomers)- essential for attachment

Functions of the Viral Functions of the Viral Capsid/EnvelopeCapsid/Envelope

Protects nucleic acidsProtects nucleic acids Help introduce the viral DNA or RNA into a Help introduce the viral DNA or RNA into a

suitable host cellsuitable host cell Stimulate the immune system to produce Stimulate the immune system to produce

antibodies that can protect the host cells antibodies that can protect the host cells against future infectionsagainst future infections

Nucleic Acids: At the Core of a Nucleic Acids: At the Core of a VirusVirus

GenomeGenome- the sum total of the genetic - the sum total of the genetic information carried by an organisminformation carried by an organism

Number of viral genes compared with a call- Number of viral genes compared with a call- quite smallquite small

They only have the genes necessary to They only have the genes necessary to invade host cells and redirect their activityinvade host cells and redirect their activity

Some viruses are exceptions to the rules re: Some viruses are exceptions to the rules re: DNA and RNADNA and RNA Parvoviruses contain single-stranded DNAParvoviruses contain single-stranded DNA Reoviruses contain double-stranded RNAReoviruses contain double-stranded RNA

DNA VirusesDNA Viruses

ssDNAssDNA dsDNAdsDNA

linearlinear circularcircular

RNA VirusesRNA Viruses

Mostly single-strandedMostly single-stranded Positive-sense RNA: genomes that are ready Positive-sense RNA: genomes that are ready

for immediate translation into proteinsfor immediate translation into proteins Negative-sense RNA: genomes have to be Negative-sense RNA: genomes have to be

converted into the proper form to be made converted into the proper form to be made into proteinsinto proteins

Segmented- individual genes exist on Segmented- individual genes exist on separate pieces of RNAseparate pieces of RNA

Other Substances in the Virus Other Substances in the Virus ParticleParticle

Other Substances in the Virus ParticleOther Substances in the Virus Particle Can contain enzymes for specific operations Can contain enzymes for specific operations

within the host cellwithin the host cell Polymerases to synthesize DNA and RNAPolymerases to synthesize DNA and RNA Replicases to copy RNAReplicases to copy RNA

6.4 How Viruses are Classified and 6.4 How Viruses are Classified and NamedNamed

Main criteriaMain criteria StructureStructure Chemical compositionChemical composition Similarities in genetic makeupSimilarities in genetic makeup

International Committee on the Taxonomy of International Committee on the Taxonomy of Viruses, 2000Viruses, 2000 3 orders3 orders 63 famillies “-viridae”63 famillies “-viridae” 263 genera “-virus”263 genera “-virus”

Some virologists use a species naming Some virologists use a species naming system, but it is not an official designationsystem, but it is not an official designation

6.5 Modes of Viral 6.5 Modes of Viral MultiplicationMultiplication

The host cell is absolutely necessary for The host cell is absolutely necessary for viral multiplicationviral multiplication

Figure 6.11

Multiplication Cycles in Animal Multiplication Cycles in Animal VirusesViruses

AdsorptionAdsorption PenetrationPenetration UncoatingUncoating SynthesisSynthesis Assembly Assembly ReleaseRelease

AdsorptionAdsorption

Virus encounters susceptible host cellsVirus encounters susceptible host cells Adsorbs specifically to receptor sites on Adsorbs specifically to receptor sites on

the cell membranethe cell membrane

• Because of the exact fit required, viruses Because of the exact fit required, viruses have a limited have a limited host rangehost range

Figure 6.12

PenetrationPenetration

Flexible cell membrane of the host is Flexible cell membrane of the host is penetrated by the whole virus or its nucleic penetrated by the whole virus or its nucleic acidacid

Endocytosis: entire virus engulfed by the Endocytosis: entire virus engulfed by the cell and enclosed in a vacuole or vesiclecell and enclosed in a vacuole or vesicle

The viral envelope can also directly fuse The viral envelope can also directly fuse with the host cell membranewith the host cell membrane

Figure 6.13

UncoatingUncoating Enzymes in the vacuole dissolve the Enzymes in the vacuole dissolve the

envelope and capsidenvelope and capsid The virus is now The virus is now uncoateduncoated

SynthesisSynthesis

Free viral nucleic acid exerts control over the Free viral nucleic acid exerts control over the host’s synthetic and metabolic machineryhost’s synthetic and metabolic machinery

DNA viruses- enter host cell’s nucleus where DNA viruses- enter host cell’s nucleus where they are replicated and assembledthey are replicated and assembled DNA enters the nucleus and is transcribed into DNA enters the nucleus and is transcribed into

RNARNA The RNA becomes a message for synthesizing The RNA becomes a message for synthesizing

viral proteins (translation)viral proteins (translation) New DNA is synthesized using host nucleotidesNew DNA is synthesized using host nucleotides

RNA viruses- replicated and assembled in the RNA viruses- replicated and assembled in the cytoplasmcytoplasm

AssemblyAssembly

Mature virus particles are constructed from Mature virus particles are constructed from the growing pool of partsthe growing pool of parts

ReleaseRelease

Nonenveloped and complex viruses are Nonenveloped and complex viruses are released when the cell lyses or rupturesreleased when the cell lyses or ruptures

Enveloped viruses are liberated by Enveloped viruses are liberated by buddingbudding or or exocytosisexocytosis

Anywhere from 3,000 to 100,000 virions Anywhere from 3,000 to 100,000 virions may be released, depending on the virusmay be released, depending on the virus

Entire length of cycle- anywhere from 8 to Entire length of cycle- anywhere from 8 to 36 hours36 hours

Figure 6.15

Damage to the Host Cell and Damage to the Host Cell and Persistent InfectionsPersistent Infections

Cytopathic effectsCytopathic effects- virus-induced - virus-induced damage to the cell that alters its damage to the cell that alters its microscopic appearancemicroscopic appearance

Inclusion bodies- compacted masses of Inclusion bodies- compacted masses of viruses or damaged cell organellesviruses or damaged cell organelles

Figure 6.16

Important for the diagnosis of viral infectionsImportant for the diagnosis of viral infections Some viral infections maintain a carrier relationshipSome viral infections maintain a carrier relationship

The cell harbors the virus and is not immediately lysedThe cell harbors the virus and is not immediately lysed Persistent infections- from a few weeks to the remainder Persistent infections- from a few weeks to the remainder

of the host’s lifeof the host’s life Some viruses remain in a chronic latent state, Some viruses remain in a chronic latent state,

periodically becoming activatedperiodically becoming activated Some viruses enter their host cell and permanently Some viruses enter their host cell and permanently

alter its genetic material, leading to canceralter its genetic material, leading to cancer Oncogenic virusesOncogenic viruses Their effect is called Their effect is called transformationtransformation OncovirusesOncoviruses- mammalian viruses capable of initiating - mammalian viruses capable of initiating

tumorstumors

Viruses that Infect BacteriaViruses that Infect Bacteria

BacteriophageBacteriophage Most contain dsDNAMost contain dsDNA Often make the bacteria they infect more Often make the bacteria they infect more

pathogenic for humanspathogenic for humans

T-even PhagesT-even Phages Icosahedral capsid head containing DNAIcosahedral capsid head containing DNA Central tube surrounded by a sheathCentral tube surrounded by a sheath CollarCollar Base plateBase plate Tail pinsTail pins FibersFibers Similar stages as animal virusesSimilar stages as animal viruses

Adsorb to host bacteriaAdsorb to host bacteria The nucleic acid penetrates the host after being injected through a The nucleic acid penetrates the host after being injected through a

rigid tube inserted through the bacterial membrane and wallrigid tube inserted through the bacterial membrane and wall Entry of the nucleic acid causes the cessation of host cell DNA Entry of the nucleic acid causes the cessation of host cell DNA

replication and protein synthesisreplication and protein synthesis The host cell machinery is then used for viral replication and The host cell machinery is then used for viral replication and

synthesis of viral proteinssynthesis of viral proteins As the host cell produces new parts, they spontaneously assembleAs the host cell produces new parts, they spontaneously assemble

Figure 6.17

Figure 6.18

Figure 6.19

Lysogeny: The Silent Virus Lysogeny: The Silent Virus InfectionInfection

Temperate phages-Temperate phages- special DNA phages special DNA phages that undergo adsorption and penetration but that undergo adsorption and penetration but are not replicated or released immediatelyare not replicated or released immediately

Instead the viral DNA enters an inactive Instead the viral DNA enters an inactive prophageprophage stage stage

LysogenyLysogeny: the cell’s progeny will also have : the cell’s progeny will also have the temperate phage DNAthe temperate phage DNA

Lysogenic conversionLysogenic conversion:: when a bacterium when a bacterium acquires a new trait from its temperate phageacquires a new trait from its temperate phage

Figure 6.20

6.6 Techniques in Cultivating and 6.6 Techniques in Cultivating and Identifying Animal VirusesIdentifying Animal Viruses

Primary purposes of viral cultivationPrimary purposes of viral cultivation To isolate and identify viruses in clinical specimensTo isolate and identify viruses in clinical specimens To prepare viruses for vaccinesTo prepare viruses for vaccines To do detailed research on viral structure, multiplication To do detailed research on viral structure, multiplication

cycles, genetics, and effects on host cellscycles, genetics, and effects on host cells Using Live Animal InoculationUsing Live Animal Inoculation

Specially bred strains of white mice, rats, hamsters, guinea Specially bred strains of white mice, rats, hamsters, guinea pigs, and rabbitspigs, and rabbits

Occasionally invertebrates or nonhuman primates are usedOccasionally invertebrates or nonhuman primates are used Animal is exposed to the virus by injectionAnimal is exposed to the virus by injection

Using Bird EmbryosUsing Bird Embryos Enclosed in an egg- nearly perfect conditions for viral Enclosed in an egg- nearly perfect conditions for viral

propagationpropagation Chicken, duck, and turkey are most commonChicken, duck, and turkey are most common Egg is injected through the shell using sterile techniquesEgg is injected through the shell using sterile techniques

Figure 6.21

Using Cell (Tissue) Culture Using Cell (Tissue) Culture TechniquesTechniques

Most viruses are propagated in some sort of Most viruses are propagated in some sort of cell culturecell culture

The cultures must be developed and The cultures must be developed and maintainedmaintained

Animal cell cultures are grown in sterile Animal cell cultures are grown in sterile chambers with special mediachambers with special media

Cultured cells grow in the form of a Cultured cells grow in the form of a monolayermonolayer

Primary or continuousPrimary or continuous

Figure 6.22

6.7 Medical Importance of 6.7 Medical Importance of Viruses Viruses

Most common cause of acute infections Most common cause of acute infections that do not result in hospitalizationthat do not result in hospitalization

Most do not cause death but those that do Most do not cause death but those that do can have very high mortality ratescan have very high mortality rates

Others can lead to long-term debilityOthers can lead to long-term debility

6.8 Other Noncellular Infectious 6.8 Other Noncellular Infectious AgentsAgents

Spongiform encephalopathiesSpongiform encephalopathies Chronic, persistent diseasesChronic, persistent diseases Long period of latencyLong period of latency Deposition of protein fibrils in the brain tissue- Deposition of protein fibrils in the brain tissue- prionsprions

Satellite virusesSatellite viruses Defective forms of virusesDefective forms of viruses Dependent on other viruses for replicationDependent on other viruses for replication

ViroidsViroids Parasitize plantsParasitize plants Very smallVery small Composed only of naked strands of RNAComposed only of naked strands of RNA

6.9 Treatment of Animal Viral 6.9 Treatment of Animal Viral InfectionsInfections

Because they are not bacteria, antibiotics Because they are not bacteria, antibiotics are ineffectiveare ineffective

Antiviral drugs block virus replication by Antiviral drugs block virus replication by targeting one of the steps in the viral life targeting one of the steps in the viral life cyclecycle

Interferon shows potential for treating and Interferon shows potential for treating and preventing viral infectionspreventing viral infections

Vaccines stimulate immunityVaccines stimulate immunity