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Lecture 29: Viruses

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Lecture outline 11/11/05

• Types of viruses– Bacteriophage

• Lytic and lysogenic life cycles

– DNA viruses– RNA viruses

• Influenza• HIV

• Prions– Mad cow disease

Figure 18.4 Viral structure

18 × 250 mm 70–90 nm (diameter) 80–200 nm (diameter) 80 × 225 nm

20 nm 50 nm 50 nm 50 nm(a) Tobacco mosaic virus (b) Adenoviruses (c) Influenza viruses (d) Bacteriophage T4

RNA

RNACapsomereof capsid

DNACapsomere

Glycoprotein Glycoprotein

Membranousenvelope

Capsid DNA

Head

Tail fiber

Tail sheath

Viral reproductive cycleVIRUS

Capsid proteins

mRNA

Viral DNA

HOST CELL

Viral DNA

DNACapsid

Figure 18.5

Entry into cell anduncoating of DNA

Replication

Transcription

Self-assemblyof newvirus particlesand their exitfrom cell

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Figure 18.4a, b

18 × 250 mm 70–90 nm (diameter)

20 nm 50 nm(a) Tobacco mosaic virus (b) Adenoviruses

RNADNACapsomere

Glycoprotein

Capsomereof capsid

A capsid is the protein shellthat encloses the viral genome

Figure 18.4d

80 × 225 nm

50 nm(d) Bacteriophage T4

DNA

Head

Tail fiber

Tail sheath

Viral Envelopes are derived fromthe membrane of the host cell

Figure 18.4c

80–200 nm (diameter)

50 nm(c) Influenza viruses

RNA

Glycoprotein

Membranousenvelope

Capsid

Bacteriophage

• Viruses of bacteria have been studiedfor decades– T1, T2, T4

• “virulent”– Lambda

• “temperate”

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See the animation

Attachment.binds to specificreceptor siteson cell surface.

Entry of phage DNAand degradation ofhost DNA.

Synthesis of viralgenomesand proteins.

Assembly ofphage capsid

Release (lysis)

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4 3

5

Phage assembly

Head Tails Tail fibers

The lytic cycle of T4

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The lytic and lysogenic cycles of phage λ

Many cell divisions produce a large population of bacteria infected with the prophage.

Replicates withhost DNA

Integrated into hostchromosome.

New phage particlessynthesized

Occasionally, a prophage exits the bacterial chromosome, initiating a lytic cycle.

Certain factorsdetermine whether

Attachment andinjection ofDNA.

Phage DNAcircularizes

Lysis and release

Lysogenic cycleLytic cycle

or Prophage

Bacterialchromosome

Phage

PhageDNA

This is a “temperate” phageClasses of Animal Viruses

Tick fevernodsRNA

Parvovirusnoss DNA

RhinovirusSARS

noyes

ss RNA(serves as mRNA)

InfluenzaEbola

yesssRNA(template)

HIVyesssRNA(retrovirus)

Herpes, chickenpox

Smallpox

No

Yes

ds DNA

ExamplesViral coatGenome Type

DNA Viruses

RNA Viruses

Smallpox

nmhm.washingtondc.museum

Influenza

Spikes of hemagglutaninAnd neuraminidase

One of the few viruses withgenome in segments (8)

“H5N1”

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The reproductive cycle of an envelopedRNA virus

Capsid and viral genomeenter cell2

The viral genome (red)functions as a template forsynthesis of complementary RNA strands (pink) by a viral enzyme.

3

New virus8

RNA

Capsid

Envelope (withglycoproteins)

Glycoproteins on the viral envelope bind to specific receptor molecules(not shown) on the host cell, promoting viral entry into the cell.

1

New copies of viralgenome RNA are madeusing complementary RNAstrands as templates.

4

Vesicles transportenvelope glycoproteins to

the plasma membrane.

6

A capsid assemblesaround each viral

genome molecule.

7

Complementary RNAstrands also function as mRNA,

which is translated into bothcapsid proteins (in the cytosol)and glycoproteins for the viral

envelope (in the ER).

5

HOST CELL

Viral genome (RNA)

Template

Capsidproteins

Glyco-proteins

mRNA

Copy ofgenome (RNA)

ER

Why are flu vaccines so hardto make?

• Flu strains are highly variable– Recombination among the viral gene

segments– RNA polymerase has high mutation

rate

• Now have some antiviral drugs(e.g. Tamiflu)– blocks the neuramidase enzyme so

virus isn’t released from cell

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HIV

www.who.int/hiv/facts/en/

The structure of HIV, the retrovirus that causesAIDS

Reversetranscriptase

Viral envelope

Capsid

Glycoprotein

RNA(two identicalstrands)

Only 9 genes in HIV:Viral coat proteinsReverse transcriptaseIntegraseProtease

HIV reproduction

New viralproteins areproduced.

6

Incorporatedinto hostchromosome.

4

New viral RNAis transcribed.

5

Makes second DNA strand.3

Reverse transcriptasesynthesizes DNA fromRNA template.

2

Virusparticles budoff.9

New capsids areassembled

8

mRNA

RNA genomefor the nextviral generation

Viral RNA

RNA-DNAhybrid

DNA

ChromosomalDNA

NUCLEUSProvirus

HOST CELL

Reverse transcriptase

New HIV leaving a cell

HIV entering a cell

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HIV Membrane of white blood cell Viral RNA enters cell

1 Reverse transcriptase is aspecial DNA polymerase

1. Copies DNA from anRNA template

2. Removes RNAtemplate

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AZT

• Azidothymidine– a modified thymidine

• The first anti-retroviral drug• Stops DNA synthesis because it does not

have a 3’OH• Originally developed as an anti cancer drug,

but too many side effects

thymidine azt Protease inhibitors-another class of drugs for HIV

Protein in active site Inhibitor in active site

www.chemistry.wustl.edu/~edudev/LabTutorials/HIV/

HIV initially produces one long polypeptide.

Protease is necessary to cut the polypeptideinto individual enzymes

Prions are infectious mis-folded proteins

Prion

Normalprotein

Originalprion

Newprion

Many prions

Starts a slow chain reaction,causing regular proteins toassume the new shape

Altered PRP proteins in nerve cells cause Mad Cow Disease