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9.1 General Properties of Viruses
• Virus: genetic element that cannot replicate independently of a living (host) cell
• Virology: the study of viruses• Virus particle (virion): extracellular form of a virus
– Exists outside host and facilitates transmission from one host cell to another
– Contains nucleic acid genome surrounded by a protein coat and, in some cases, other layers of material
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9.1 General Properties of Viruses
• Viral Genomes (Figure 9.1)– Either DNA or RNA genomes
– Some circular, but most linear
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Figure 9.1
Viral Class
Viral Genome
DNA viruses RNA virusesRNA DNA
viruses
ssDNA dsDNA ssRNA dsRNAssRNA
(Retroviruses)dsDNA
(Hepadnaviruses)
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9.2 Nature of the Virion
• Viral Structure– Capsid: the protein shell that surrounds the
genome of a virus particle (Figure 9.2)• Composed of a number of protein molecules
arranged in a precise and highly repetitive pattern around the nucleic acid
– Capsomere: subunit of the capsid• Smallest morphological unit visible with an
electron microscope
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Figure 9.218 nm
Virus RNA
Structural subunits(capsomeres)
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9.2 Nature of the Virion
• Viral Structure (cont’d)– Nucleocapsid: complete complex of nucleic acid
and protein packaged in the virion (Figure 9.3)
– Enveloped virus: virus that contains additional layers around the nucleocapsid
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Figure 9.3
Nucleocapsid
Nucleicacid
Capsid(composed ofcapsomeres)
Envelope
Capsid
Nucleic acid
Naked virus Enveloped virus
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9.2 Nature of the Virion
• Nucleocapsids constructed in highly symmetric ways
– Helical symmetry: rod-shaped viruses (e.g., tobacco mosaic virus)
• Length of virus determined by length of nucleic acid
• Width of virus determined by size and packaging of protein subunits
– Icosahedral symmetry: spherical viruses (e.g., human papillomavirus; Figure 9.4)
• Most efficient arrangement of subunits in a closed shell
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Figure 9.4
5-Fold 3-Fold 2-FoldSymmetry
Cluster of5 units
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9.2 Nature of the Virion
• Enveloped Viruses (Figure 9.5a)– Have membrane surrounding nucleocapsid
• Lipid bilayer with embedded proteins
– Envelope makes initial contact with host cell
• Complex Viruses (Figure 9.5b)– Virions composed of several parts, each with
separate shapes and symmetries
– Bacterial viruses contain complicated structures• Icosahedral heads and helical tails
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Figure 9.5
Collar
Tail
Endplate
Tail pins
Tail fibers
Head
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9.2 Nature of the Virion
• Some virions contain enzymes critical to infection– Lysozyme
• Makes hole in cell wall• Lyses bacterial cell
– Nucleic acid polymerases
– Neuraminidases• Enzymes that cleave glycosidic bonds• Allows liberation of viruses from cell
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9.3 The Virus Host
• Viruses replicate only in certain types of cells or in whole organisms
• Bacterial viruses are easiest to grow; model systems
• Animal viruses (and some plant viruses) can be cultivated in tissue or cell cultures
• Plant viruses typically are most difficult because study often requires growth of whole plant
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9.4 Quantification of Viruses
• Titer: number of infectious units per volume of fluid
• Plaque assay: analogous to the bacterial colony; one way to measure virus infectivity (Figure 9.6)
– Plaques are clear zones that develop on lawns of host cells
• Lawn can be bacterial or tissue culture (Figure 9.7)• Each plaque results from infection by a single virus
particle
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Figure 9.6
Nutrient agarplate
Sandwich of topagar andnutrient agar
Lawn of hostcells
Phageplaques
Plaques
Mixture containingmolten top agar,bacterial cells, anddiluted phagesuspension
Pour mixture ontosolidified nutrientagar plate
Let solidify
Incubate
© 2012 Pearson Education, Inc.
9.5 General Features of Virus Replication
• Phases of Viral Replication (Figure 9.8)– Attachment (adsorption) of the virus to a
susceptible host cell
– Entry (penetration) of the virion or its nucleic acid
– Synthesis of virus nucleic acid and protein by cell metabolism as redirected by virus
– Assembly of capsids and packaging of viral genomes into new virions (maturation)
– Release of mature virions from host cell
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Figure 9.8
Protein coatremains outside
Viral DNA enters
Virion
DNA
Cell (host)
Virions
Attachment(adsorption)
Penetration(injection)
Synthesis ofnucleic acidand protein
Assembly andpackaging
Release(lysis)
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9.5 General Features of Virus Replication
• Virus replication typically characterized by a one-step growth curve (Figure 9.9)
• Latent period: eclipse + maturation• Burst size: number of virions released
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Figure 9.9
Eclipse Maturation
Earlyenzymes
Nucleicacid
Proteincoats
Virusadded
Latent period
Assemblyandrelease
Time
Rel
ativ
e vi
rus
cou
nt
(pla
qu
e-fo
rmin
g u
nit
s)
© 2012 Pearson Education, Inc.
9.6 Viral Attachment and Penetration
• Attachment of virion to host cell is highly specific– Requires complementary receptors on the
surface of a susceptible host and its infecting virus
– Receptors on host cell carry out normal functions for cell (e.g., uptake proteins, cell to cell interaction)
– Receptors include proteins, carbohydrates, glycoproteins, lipids, lipoproteins, or complexes
© 2012 Pearson Education, Inc.
9.6 Viral Attachment and Penetration
• The attachment of a virus to its host cell results in changes to both virus and cell surface that facilitate penetration
• Permissive cell: host cell that allows the complete replication cycle of a virus to occur
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9.6 Viral Attachment and Penetration
• Bacteriophage T4: virus of E. coli; one of the most complex penetration mechanisms (Figure 9.10)
– Virions attach to cells via tail fibers that interact with polysaccharides on E. coli cell envelope
– Tail fibers retract and tail core makes contact with E. coli cell wall
– Lysozyme-like enzyme forms small pore in peptidoglycan
– Tail sheath contracts and viral DNA passes into cytoplasm
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Figure 9.10
Tailfibers
Tail pins
Outermembrane
Peptidoglycan
Cytoplasmicmembrane
Cytoplasm
Taillysozyme
T4 genome
© 2012 Pearson Education, Inc.
9.6 Viral Attachment and Penetration
• Many eukaryotes possess mechanisms to diminish viral infections
– For example, immune defense mechanisms, RNA interference
• Prokaryotes also possess mechanisms– CRISPR
• Similar to RNA interference
– Restriction modification system
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9.6 Viral Attachment and Penetration
• Restriction modification systems (cont’d)– DNA destruction system; only effective
against double-stranded DNA viruses
– Restriction enzymes (restriction endonucleases) cleave DNA at specific sequences
– Modification of host’s own DNA at restriction enzyme recognition sites prevents cleavage of own DNA
© 2012 Pearson Education, Inc.
9.6 Viral Attachment and Penetration
• Viral mechanisms to evade bacterial restriction systems– Chemical modification of viral DNA (glycosylation
or methylation)
– Production of proteins that inhibit host cell restriction system
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Figure 9.11
dsDNA () virusClass I
Class VII
ssDNA () virus
Class II
dsRNA () virus
Class III
ssRNA () virus
Class IV
ssRNA () virus
Class V
ssRNA () retrovirusClass VI
dsDNA intermediate
dsDNA intermediate
Synthesis ofother strand
Transcriptionof minus strand
Transcriptionof minus strand
Transcriptionof minus strand
Transcriptionof minus strand
Used directlyas mRNA
Reversetranscription
mRNA () mRNA ()
Genomereplication: Class I, Class II,
Class VII, DNA viruses
Genomereplication: Class III, Class IV, Class V, Class VI,
RNA viruses
classical semiconservativeclassical semiconservative,discard () strand transcription followed byreverse transcription
make ssRNA () and transcribe from this to give ssRNA () partnermake ssRNA () and transcribe from this to give ssRNA () genomemake ssRNA () and transcribe from this to give ssRNA () genomemake ssRNA () genome by transcription of () strand of dsDNA
© 2012 Pearson Education, Inc.
9.7 Production of Viral Nucleic Acid and Protein
• Once a host has been infected, new copies of the viral genome must be made and virus-specific proteins synthesized in order for the virus to replicate
• Generation of messenger RNA (mRNA) occurs first
• Viral genome serves as template for viral mRNA• In some RNA viruses, viral RNA itself is the mRNA• In some cases essential transcriptional enzymes
are contained in the virion
© 2012 Pearson Education, Inc.
9.7 Production of Viral Nucleic Acid and Protein
• Nomenclature used to describe mRNA is used to describe the configuration of the genome of a single-stranded DNA or RNA virus (mRNA is said to be in plus (+) configuration; its complement is in minus () configuration)
– Positive-strand RNA virus: single-stranded RNA genome with same orientation as its mRNA
– Negative-strand RNA virus: single-stranded RNA genome with orientation complementary to its mRNA
© 2012 Pearson Education, Inc.
9.7 Production of Viral Nucleic Acid and Protein
• Retroviruses: animal viruses responsible for causing certain types of cancers and acquired immunodeficiency syndrome (AIDS)– Class VI and VII viruses
– Require reverse transcriptase
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9.7 Production of Viral Nucleic Acid and Protein
• Viral Proteins– Production follows synthesis of viral mRNA
• Early proteins – synthesized soon after infection
– necessary for replication of virus nucleic acid
– typically act catalytically
– synthesized in smaller amounts
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9.7 Production of Viral Nucleic Acid and Protein
• Production of Viral Proteins (cont’d)– Late proteins
• Synthesized later • Include proteins of virus coat• Typically structural components• Synthesized in larger amounts
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9.8 Overview of Bacterial Viruses
• Bacteriophages are very diverse (Figure 9.12)• Best-studied bacteriophages infect enteric
bacteria– Examples of hosts: E. coli, Salmonella enterica
• Most phages contain dsDNA genomes• Most are naked, but some possess lipid
envelopes• They are structurally complex, containing heads,
tails, and other components
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Figure 9.12
RNA
ssDNA
dsDNA
MS2ss ds 6
174fd, M13
T3, T7
MuLambda T2, T4
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9.10 Temperate Bacteriophages, Lambda, and P1
• Temperate viruses: can undergo a stable genetic relationship within the host (Figure 9.16)
– But can also kill cells through lytic cycle
• Lysogeny: state where most virus genes are not expressed and virus genome (prophage) is replicated in synchrony with host chromosome
• Lysogen: a bacterium containing a prophage• Under certain conditions lysogenic viruses may
revert to the lytic pathway and begin to produce virions
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Figure 9.16Temperate virus
Lytic pathway Lysogenic pathway
Induction
Viral DNA
Host DNA
Cell (host)
Lysogenized cell
Attachment
Injection
Viral DNAreplicates
Coat proteinssynthesized;virus particlesassembled
Viral DNAis integratedinto host DNA
Lysis Celldivision
Prophage
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Figure 9.17
Capsid
Tail
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9.11 Overview of Animal Viruses
• Entire virion enters the animal cell, unlike in prokaryotes
• Eukaryotic cells contain a nucleus, the site of replication for many animal viruses
• Animal viruses contain all known modes of viral genome replication (Figure 9.21)
• Many more kinds of enveloped animal viruses than enveloped bacterial viruses exist– As animal viruses leave host cell, they can
remove part of host cell’s lipid bilayer for their envelope
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Figure 9.21
DNA viruses RNA viruses
Nonenveloped Enveloped Nonenveloped Enveloped all ssRNA
ssDNAParvovirus
dsDNAPapovavirus
dsDNA
Adenovirus
dsDNA
Iridovirus
partiallydsDNA
Hepadnavirus
dsDNA
Poxvirus
dsDNA
Herpesvirus
100 nm
100 nm
dsRNA
ssRNAPicornavirus
Reovirus
Rhabdovirus
Togavirus
Orthomyxovirus
Bunyavirus Coronavirus
Arenavirus RetrovirusParamyxovirus
© 2012 Pearson Education, Inc.
9.11 Overview of Animal Viruses
• Consequences of Virus Infection in Animal Cells (Figure 9.22)
– Persistent infections: release of virions from host cell does not result in cell lysis
• Infected cell remains alive and continues to produce virus
– Latent infections: delay between infection by the virus and lytic events
– Transformation: conversion of normal cell into tumor cell
– Cell fusion: two or more cells become one cell with many nuclei
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Figure 9.22
Transformation
Lysis
Persistentinfection
Latentinfection
Cell
Virus
Attachmentand penetration
Virusmultiplication
May
rev
ert
to ly
tic
infe
ctio
n
Transformationinto tumor cell
Tumorcelldivision
Cellfusion
Death ofcell andreleaseof virus
Slow releaseof virus withoutcell death
Virus presentbut not replicating
© 2012 Pearson Education, Inc.
9.12 Retroviruses
• Retroviruses: RNA viruses that replicate through a DNA intermediate
– Enveloped viruses (Figure 9.23a)
– Contain a reverse transcriptase (copies information from its RNA genome into DNA), integrase, and protease
– Virion contains specific tRNA molecules
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Figure 9.23a
Surface envelope protein
Transmembraneenvelope protein
RNAEnzymes(reversetranscriptase,integrase,protease)
Lipidmembranebilayer
Core shellprotein
Core protein
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9.12 Retroviruses
• Retroviruses have a unique genome– Two identical ssRNA molecules of the plus (+)
orientation
– Contain specific genes (Figure 9.23b)• gag: encode structural proteins• pol: encode reverse transcriptase and
integrase• env: encode envelope proteins
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9.12 Retroviruses
• Process of Replication of a Retrovirus (Figure 9.24)
– Entrance into the cell
– Removal of virion envelope at the membrane
– Reverse transcription of one of the two RNA genomes
– Integration of retroviral DNA into host genome
– Transcription of retroviral DNA
– Assembly and packaging of genomic RNA
– Budding of enveloped virions; release from cell
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Figure 9.24Retrovirus virioncontaining ssRNA(two copies)
R RssRNA
LTR
LTRdsDNA
Host DNA
LTR LTRProvirus
ssRNAR R Viral mRNA and
genomic RNA
ssRNA Nucleocapsid
Host cytoplasmicmembrane
Progenyretrovirus virions
Entrance
Uncoating
Reverse transcription
Travel to nucleus andintegration into host DNA
Transcription
Encapsidation
Budding
Release
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IV. Subviral Entities
• 9.13 Defective Viruses• 9.14 Viroids• 9.15 Prions
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9.13 Defective Viruses
• Defective viruses: viruses that are parasitic on other viruses– Require other virus (helper virus) to provide
some function• Some rely on intact virus of same type• Satellite viruses: defective viruses for which
no intact version exists; rely on unrelated viruses as helpers
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9.14 Viroids
• Viroids: infectious RNA molecules that lack a protein coat
– Smallest known pathogens (246–399 bp)
– Cause a number of important plant diseases (Figure 9.25)
– Small, circular, ssRNA molecules (Figure 9.26)
– Do not encode proteins; completely dependent on host-encoded enzymes
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Figure 9.25
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Figure 9.26
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9.15 Prions
• Prions: infectious proteins whose extracellular form contains no nucleic acid
– Known to cause disease in animals (transmissible spongiform encephalopathies)
– Host cell contains gene (PrnP) that encodes native form of prion protein that is found in healthy animals (Figure 9.28)
– Prion misfolding results in neurological symptoms of disease (e.g., resistance to proteases, insolubility, and aggregation)
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Figure 9.28Neuronal cell
Nucleus
DNA
Normalfunction
Abnormalfunction
PrPSc
(misfolded prion)
PrPc
(normal prion)
PrPSc-inducedmisfolding
TranslationTranscription
Prnp
© 2012 Pearson Education, Inc.
9.15 Prions
• Prion disease occurs by three distinct mechanisms:
– Infectious prion disease: pathogenic form of prion protein is transmitted between animals or humans
– Sporadic prion disease: random misfolding of a normal, healthy prion protein in an uninfected individual
– Inherited prion disease: mutation in prion gene yields a protein that changes more often into disease-causing form
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