Post on 21-Dec-2015
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
CapsidDNA
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-assembly of new virus particles and their exit from cell
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 shell that 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 from the 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 studied for decades– T1, T2, T4
• “virulent”
– Lambda• “temperate”
0.5 m
See the animation
Attachment. binds to specificreceptor sites on cell surface.
Entry of phage DNA
and degradation of host DNA.
Synthesis of viral genomes and proteins.
Assembly of phage capsid
Release (lysis)
12
4 3
5
Phage assembly
Head Tails Tail fibers
The lytic cycle of T4
The lytic and lysogenic cycles of phage
Many cell divisions produce a large population of bacteria infected with the prophage.
Replicates with host DNA
Integrated into host chromosome.
New phage particles synthesized
Occasionally, a prophage exits the bacterial chromosome, initiating a lytic cycle.
Certain factorsdetermine whether
Attachment and injection of DNA.
Phage DNAcircularizes
Lysis and release
Lysogenic cycleLytic cycle
or Prophage
Bacterialchromosome
Phage
PhageDNA
This is a “temperate” phage
Classes of Animal VirusesGenome Type Viral coat Examples
ds DNA No
Yes
Herpes, chickenpox
Smallpox
ss DNA no Parvovirus
dsRNA no Tick fever
ss RNA
(serves as mRNA)
no
yes
Rhinovirus
SARS
ssRNA
(template)
yes Influenza
Ebola
ssRNA
(retrovirus)
yes HIV
DNA Viruses
RNA Viruses
Influenza
Spikes of hemagglutaninAnd neuraminidase
One of the few viruses with genome in segments (8)
“H5N1”
The reproductive cycle of an enveloped RNA 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 hard to 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
The structure of HIV, the retrovirus that causes AIDS
Reversetranscriptase
Viral envelope
Capsid
Glycoprotein
RNA(two identicalstrands)
Only 9 genes in HIV:Viral coat proteinsReverse transcriptaseIntegraseProtease
HIV reproduction
New viral proteins are produced.
6
Incorporated into host chromosome.
4
New viral RNA is transcribed.
5
Makes second DNA strand.3
Reverse transcriptase synthesizes DNA from RNA template.
2
Virus particles bud off.
9New capsids are assembled
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
0.25 µm
HIV Membrane of white blood cell Viral RNA enters cell
1
Reverse transcriptase is a special DNA polymerase
1. Copies DNA from an RNA template
2. Removes RNA template
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 polypeptide into individual enzymes