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    Georgia briefly tops chart for flureports

    Monday, October 26th, 2015

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    Chapter 6 Introduction

    All life-forms can be infected by viruses.

    Some viruses generate seriousepidemics, from dengue feverto influenza to AIDS.

    - thers fill essential nichesin the environment,

    particularly inmarine ecosystems.

    In research, viruses haveprovided both tools andmodel systems inmolecular biology.

    Figure 6.1

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    6.! "hat Is a #irus$

    A virusis a noncellular particle that must infect ahost cell, %here it reproduces.

    - It typically subverts the cell&s machinery and directs it

    to produce viral particles.

    'he virus particle, or virion, consists of a singlenucleic acid (D)A or *)A+ contained %ithin a

    protective protein capsid.

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    #iruses are ubiuitous in all environments

    #iruses are part of our daily lives

    - ost freuent infections of college students

    - *espiratory pathogens such as rhinovirus (the commoncold+ and /pstein-0arr virus (infectious mononucleosis+

    - Se1ually transmitted viruses such as herpes simple1virus (2S#+ and papillomavirus (genital %arts+

    Different viruses infect every group of organisms- /ach species of virus infects a particular group of

    host species, or host range

    #iruses Infect All 3orms of 4ife

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    Figure 6.3

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    Figure 6.3Why are there

    holes on the

    growth medium

    where bacteria

    mixed with lytic

    phage was spread?

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    'he propagation of viruses is mimic5ed by thespread of computer viruses,7 %hose informationinfects7 computer memory.

    #iral 8enomes

    Figure 6.4

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    Small viruses commonlyhave a small genome,encoding under ten genes

    - 'he genes may actuallyoverlap in seuence

    Figure 6.5

    4arge viruses may havemore than !99 genes

    - Indeed, mimivirus encodesover !,999 genes

    Figure 6.6

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    Small viruses commonlyhave a small genome,encoding under ten genes

    - 'he genes may actuallyoverlap in seuence

    Figure 6.5

    4arge viruses may havemore than !99 genes

    - Indeed, mimivirus encodesover !,999 genes

    Figure 6.6

    What type

    o# proteins

    are

    encoded

    by the

    cauli#lower

    $irus $s% amimi$irus?

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    Viroidsare *)A molecules that infect plants. 'hey have no protein capsid.

    - Are replicated by host *)A polymerase.

    - Some have catalytic ability.

    #iroids

    Figure 6.7

    'hrysanthemum in#ected by

    'hrysanthemum stunt $iroid (')*d+

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    Prionsare proteins that infect animals. 'hey have no nucleic acid component.

    - 2ave an abnormal structure that alters theconformation of other normal proteins

    :rions

    Figure 6.8

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    Prion History

    18thcentury scrapie

    affecting sheep is documented

    1920s neurologists Creutzfeldt andJakob discover similar disease in man 190s !a"dusek studies kuru spread

    by cannibalistic rituals in ne# !uinea $on %obel &rize in 19'

    1990s mad co# disease in !reat(ritain causing 1'0 deaths

    199' %obel &rize a#arded to )tanley&ursiner for identifying prions

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    Transmissible Spongiform

    Encephalophathy )ymptoms

    *ost associated #ith Creutzfeldt+Jakobdisease ,CJ-.

    (ehavior changes/ aniety/ insomnia *uscle "erks/ memory loss/ demenia

    gent &rions + &r&

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    Transmissible SpongiformEncephalophathy

    &athogenesis &rions promotes ,.

    misfolding of normalproteins on neuralsurface

    3ventually causetissue damage

    4ransmission Corneal transplants/

    contaminatedinstruments/hormone in"ections

    Can be transmittedfrom cattle #ithcontaminated meat

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    Effects of Prion Infection

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    Prion Generation

    %& or &r&c

    %ormal proteins

    && or &r&)c

    *isfolded &r&cproteins 5arious theories remain about ho# a

    &r&Cis formed 6esistant to7

    -isinfectants eat and 5 6adiation

    -eleaulta/ %: 6: et. al., ;solation of phosphatidylethanolamine as a solitary cofactor for prionformation in the absence of nucleic acids/ &%)/ 2012/ 10978

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    Prion Diseases

    $hat other disease may beassociated #ith prions that #e haveyet to confirm

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    Prion Diseases

    $hat other disease may beassociated #ith prions that #e haveyet to confirm

    lzheimer>s &arkinson>s *ultiple system atrophy ,*).

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    6.; #irus Structure

    'he viral capsidis composed of repeated proteinsubunits.

    - 'his ma1imizes the capacity %hile minimizing the

    reuired number of genes.

    'he capsid pac5ages the viral genome anddelivers it into the host cell.

    Different viruses ma5e different capsid forms.- 'hese can be divided into symmetricaland

    asymmetrical types.

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    Icosahedral viruses- Are polyhedral %ith ;9 identical triangular faces

    Symmetrical #iruses

    Figure 6.9

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    In some icosahedral viruses, the capsid isenclosed in an envelope, formed from the cell

    membrane.- 'he envelope contains glycoprotein spikes, %hich are encoded

    by the virus.

    - 0et%een the envelope and capsid, teguentproteins may be

    found.

    Figure 6.1!

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    Filaentous viruses

    - 'he capsid consists of a long tube of protein, %ith the

    genome coiled inside- #ary in length, depending on genome size

    - Include bacteriophages as %ell as animal viruses

    Figure 6.11

    A

    B

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    3ilamentous viruses sho% helical symmetry

    - 'he pattern of capsid monomers forms a helical tube

    around the genome, %hich usually %inds helically%ithin the tube.

    Figure 6.1"

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    'hese have comple1 multipart structures

    #4 $acteriophages- 2ave an icosahedral head7 and helical nec57

    Asymmetrical #iruses

    Figure 6.13

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    Po% viruses- 'heir genome is surrounded by several layers

    -

    A core envelope studded %ith spi5e proteins- An outer membrane

    - Also contain a large number of accessory proteins

    Figure 6.14

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    6.< #iral 8enomes and Classification

    #iral genomes can be

    - D)A or *)A

    - Single- or double-stranded (ss or ds+

    - 4inear or circular

    Include genes encoding viral proteins

    - Capsid

    - /nvelope proteins (if need be+

    - Any polymerase not found in host cell

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    6.< #iral 8enomes and Classification

    #iral genomes can be

    - D)A or *)A

    - Single- or double-stranded (ss or ds+

    - 4inear or circular

    Include genes encoding viral proteins

    - Capsid

    - /nvelope proteins (if need be+

    - Any polymerase not found in host cell

    Whatcellularcomponentis missingfrom

    viruses?

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    2!

    ,o ,hin- .bout

    Why would a $irus want to bring to its host a

    uni/ue polymerase?

    0int ,hin- about $iral genomes

    bola $irus

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    'he International Committee on 'a1onomy of#iruses (IC'#+ has devised a classificationsystem, based on several criteria

    - &enoe coposition

    - 'apsid s(etr(

    - )nvelope

    - *i+e o, the virion

    - -ost range

    'he International Committee on

    'a1onomy of #iruses

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    So far, the genome composition and mechanismsof replication and m*)A e1pression define

    seven fundamental groups of viral species- &roup I dou$le/stranded 02

    - &roup II single/stranded 02

    -&roup III dou$le/stranded 2

    - &roup IV single/stranded 2

    - &roup V single/stranded 2

    -&roup VI 2 retroviruses

    - &roup VII 02 pararetroviruses

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    Figure 6.152

    *irions do notcontain

    ribosomes

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    Figure 6.152

    *iral

    proteins

    *irions do notcontain

    ribosomes

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    ,hin- this out some more

    What parts o# a $irus must be reproduced to

    ma-e more $iruses?

    What in the host cell ma-es .? m.?

    proteins?

    What about single stranded .? r double

    stranded . genomes?

    Fi 6 152

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    Figure 6.152

    Fi 6 152

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    Figure 6.152

    6 = #i l * li ti ith

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    6.= #iral *eplication %ith

    /mphasis on 0acteriophage

    All viruses reuire a host cell for reproduction.

    - 'hus, they all face the same needs for host infection

    - -ost recognition and attachent

    - &enoe entr(

    - 2sse$l( o, virions

    - )%it and transission

    0acteriophage are viruses that infect bacterialcells

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    Contact and attachment are mediated by cell/sur,ace receptors.

    - :roteins that are specific to the host species and%hich bind to a specific viral component.

    - 0acterial cell receptorsare normally used forimportant functions forthe host cell.

    - /1ample sugar upta5e

    0acteriophages Attach to 2ost Cells

    Figure 6.18

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    ost bacteriophages (phages+ in>ect only theirgenome into a cell through the cell envelope.

    - 'he phage capsid remains outside, attached to the cellsurface.

    :hage *eproduction %ithin 2ost Cells

    Figure 6.192

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    emember?

    What are two ways bacterial cells can de#end

    themsel$es #rom a phage in#ection?

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    0acteriophages can undergo t%o different types oflife cycles

    1. (tic c(cle

    0acteriophage uic5ly replicates, 5illing host cell

    ". (sogenic c(cle

    0acteriophage is uiescent.

    Integrates into cell chromosome, as a prophage

    Can reactivate to become lytic

    'he decision7 bet%een the t%o cycles is dictated

    by environmental cues In general, events that threaten host cell survival trigger a

    lytic burst

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    Current pplications of

    !ytic Phage !ab

    Phage "isplay for protein engineering

    #e"ical Phage therapy

    Treatment of antibiotic resistant infections

    $ith specific lytic phage

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    Phage Therapy "vances

    Phage therapy centers in Georgia %formerly ofthe Soviet &nion' Creates lytic phage coc(tails that target

    specific antibiotic resistant bacteria

    Phagoburn European Commission "e"icates )*+,

    million in ,-./ Phage treatment of burn victims suffering

    from infecte" $oun"s

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    Phage Therapy

    .+ What $oul" be the a"vantage of using phage therapy forbacterial infections?

    ,+ What $oul" be the "isa"vantage of using phage therapy in

    humans?/+ What other applications coul" be use" for phage therapy asi"e

    from human infections?

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    0ther Potential pplications

    1oo" applications1resh cut fruit

    #eat an" poultry pro"ucts

    Currently available2 !istShiel"3 a phage coc(tail that targets Listeriamonocytogenes

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    nimation2lysis and lysogeny

    7ysis and 7ysogeny

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    :hages use host cell machinery to synthesize capsids

    'hey then assemble progeny phages

    /1it from cell- (sis

    - a5e enzyme that brea5s do%n cell %all

    - 2ost cell bursts to release progeny phage- *lo release

    - 3ilamentous phages can e1trude individual progenythrough cell envelope

    - 2ost cells gro% slo%ly but do not die

    Figure 6 "!

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    Figure 6."!

    0 t i l 2 t D f

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    0acteria have evolved several forms of defense

    against bacteriophage infection- &enetic resistance

    - Altered receptor proteins

    - estriction endonucleases- Cleave viral D)A lac5ing methylation

    - 'I*Pintegration of phage D)A seuences

    -Clustered regularly interspaced short palindromic repeats

    - A bacterial immune system of sorts

    0acterial 2ost Defenses

    6 ? Animal and

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    6.? Animal and

    :lant #irus *eplication

    Animal and plant viruses solve problems similar tothose faced by bacteriophages

    - 2ost attachment, genome entry and gene e1pression,

    virion assembly, and virion release 2o%ever, eu5aryotic cells have a more comple1

    structure than pro5aryotic cells

    -'herefore, animal and plant viruses have greatercomple1ity and diversity of viral replication cyclesthan %e see in bacteriophages

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    A i l #i Sh 'i ' i

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    Animal viruses bind specific receptor proteins on

    their host cell.- *eceptors determine the viral tropis.

    - /bola virus e1hibits broad tropism, infecting many 5indsof host tissues.

    - :apillomavirus sho%s tropism for only epithelial tissues.

    ost animal viruses enter host as virions.

    - Internalized virions undergo uncoating, %heregenome is released from its capsid.

    - Can occur in several different %ays.

    Animal #iruses Sho% 'issue 'ropism

    A i l #i * li ti C l

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    'he primary factor determining the life cycle of an animal

    virus is the form of its genome. 02 viruses

    - Can utilize the host replication machinery

    2 viruses- @se an *)A-dependent *)A-polymerase to transcribe their

    m*)A

    etroviruses

    - @se a reverse transcriptase to copy their genomic seuence intoD)A for insertion in the host chromosome

    Animal #irus *eplication Cycles

    A i l #i * li ti C l

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    All animal viruses ma5e proteins %ith hostribosomes

    - 'ranslation occurs in the cytoplasm.

    Assembly of ne% virions

    - Capsid and genome

    - ay occur in the cytoplasm or nucleus

    - /nvelope proteins are inserted into a membrane

    - Cell membrane or organelle membrane

    Animal #irus *eplication Cycles

    Animal #ir s *eplication C cles

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    *elease of progeny viruses from host cell

    - 4ysis of cell

    - 0udding

    - #irus passes through membrane

    - embrane lipids surround capsid to form envelope

    - All enveloped viruses bud from a membrane

    - /ither plasma membrane or organelle membrane

    Animal #irus *eplication Cycles