Download Viral reproductive cycle

Lecture 29: Viruses
Lecture outline 11/11/05
• Types of viruses
– Bacteriophage
• Lytic and lysogenic life cycles
– DNA viruses
– RNA viruses
• Influenza
• HIV
• Prions
– Mad cow disease
0.5 µm
Figure 18.4 Viral structure
Capsomere
of capsid
RNA
Capsomere
Viral reproductive cycle
Membranous
envelope
DNA
Head
Capsid Tail
sheath
RNA
DNA
18 × 250 mm
20 nm
(a) Tobacco mosaic virus
Entry into cell and
uncoating of DNA
Replication
50 nm
(b) Adenoviruses
Transcription
Viral DNA
Glycoprotein
70–90 nm (diameter)
VIRUS
HOST CELL
Tail
fiber
Glycoprotein
DNA
Capsid
mRNA
80–200 nm (diameter)
50 nm
(c) Influenza viruses
80 × 225 nm
Viral DNA
50 nm
(d) Bacteriophage T4
Figure 18.5
Capsid
proteins
Self-assembly
of new
virus particles
and their exit
from cell
1
A capsid is the protein shell
that encloses the viral genome
Capsomere
of capsid
Viral Envelopes are derived from
the membrane of the host cell
Membranous
envelope
RNA
Capsomere
DNA
Head
Tail
sheath
Capsid
DNA
RNA
Tail
fiber
18 × 250 mm
Glycoprotein
Glycoprotein
70–90 nm (diameter)
20 nm
50 nm
Figure 18.4a, b (a) Tobacco mosaic virus (b) Adenoviruses
Figure 18.4d
80–200 nm (diameter)
80 × 225 nm
50 nm
(d) Bacteriophage T4
Figure 18.4c
50 nm
(c) Influenza viruses
The lytic cycle of T4
Bacteriophage
1
• Viruses of bacteria have been studied
for decades
Attachment.
binds to specific
receptor sites
on cell surface.
2
5
Entry of phage DNA
and degradation of
host DNA.
Release (lysis)
– T1, T2, T4
• “virulent”
Phage assembly
– Lambda
• “temperate”
0.5 µm
4
See the animation
Head Tails Tail fibers
Assembly of
phage capsid
3
Synthesis of viral
genomes
and proteins.
2
The lytic and lysogenic cycles of phage λ
Attachment and
injection of
DNA.
Phage
DNA
This is a “temperate” phage
Phage DNA
circularizes
Phage
Occasionally, a prophage
exits the bacterial chromosome,
initiating a lytic cycle.
Bacterial
chromosome
RNA Viruses
Certain factors
determine whether
Prophage
or
New phage particles
synthesized
Genome Type
Viral coat
Examples
ds DNA
No
Herpes, chickenpox
DNA Viruses
Lysogenic cycle
Lytic cycle
Lysis and release
Many cell divisions
produce a large
population of bacteria
infected with the
prophage.
Classes of Animal Viruses
Replicates with
host DNA
Integrated into host
chromosome.
Smallpox
Yes
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
Influenza
One of the few viruses with
genome in segments (8)
“H5N1”
nmhm.washingtondc.museum
Spikes of hemagglutanin
And neuraminidase
3
The reproductive cycle of an enveloped
RNA virus
1 Glycoproteins on the viral envelope
bind to specific receptor molecules
(not shown) on the host cell,
promoting viral entry into the cell.
Capsid
RNA
Envelope (with
glycoproteins)
2 Capsid and viral genome
enter cell
HOST CELL
3 The viral genome (red)
Viral genome (RNA)
Template
5 Complementary RNA
strands also function as mRNA,
which is translated into both
capsid proteins (in the cytosol)
and glycoproteins for the viral
envelope (in the ER).
functions as a template for
synthesis of complementary
RNA strands (pink) by a viral
enzyme.
mRNA
Capsid
proteins
ER
Glycoproteins
Copy of
genome (RNA)
4 New copies of viral
genome RNA are made
using complementary RNA
strands as templates.
6 Vesicles transport
envelope glycoproteins to
the plasma membrane.
8 New virus
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
7 A capsid assembles
around each viral
genome molecule.
4
The structure of HIV, the retrovirus that causes
AIDS
HIV
Only 9 genes in HIV:
Viral coat proteins
Reverse transcriptase
Integrase
Protease
Glycoprotein
Viral envelope
Capsid
Reverse
transcriptase
www.who.int/hiv/facts/en/
HIV reproduction
HIV
Membrane of
white blood cell
1
Viral RNA enters cell
Reverse transcriptase
2
synthesizes
DNA from
RNA template
.
HOST CELL
3
Reverse
transcriptase
RNA
(two identical
strands)
Reverse transcriptase is a
special DNA polymerase
Makes second DNA strand.
Viral RNA
RNA-DNA
hybrid
4 Incorporated
into host
chromosome.
0.25 µm
HIV entering a cell
DNA
NUCLEUS
Chromosomal
DNA
RNA genome
for the next
viral generation
Provirus
5
New viral RNA
is transcribed.
1. Copies DNA from an
RNA template
2. Removes RNA
template
mRNA
6
New viral
proteins are
produced.
New HIV leaving a cell
Virus
9
particles
bud
off.
8
New capsids are
assembled
5
thymidine
Protease inhibitorsanother class of drugs for HIV
azt
AZT
Protein in active site
Inhibitor in active site
• 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
HIV initially produces one long polypeptide.
Protease is necessary to cut the polypeptide
into individual enzymes
www.chemistry.wustl.edu/~edudev/LabTutorials/HIV/
Prions are infectious mis-folded proteins
Prion
Original
prion
Many prions
Normal
protein
New
prion
Starts a slow chain reaction,
causing regular proteins to
assume the new shape
Altered PRP proteins in nerve cells cause Mad Cow Disease
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