figure 18.4 viral structure viral reproductive cycledstratto/bcor011_handouts/29_viruses.pdf · 4...
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Lecture 29: Viruses
0.5 µm
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”
0.5 µm
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.
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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.
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New copies of viralgenome RNA are madeusing complementary RNAstrands as templates.
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Vesicles transportenvelope glycoproteins to
the plasma membrane.
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A capsid assemblesaround each viral
genome molecule.
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Complementary RNAstrands also function as mRNA,
which is translated into bothcapsid proteins (in the cytosol)and glycoproteins for the viral
envelope (in the ER).
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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.
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Incorporatedinto hostchromosome.
4
New viral RNAis transcribed.
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Makes second DNA strand.3
Reverse transcriptasesynthesizes DNA fromRNA template.
2
Virusparticles budoff.9
New capsids areassembled
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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