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Chapter 19
Viruses
Microbial Model Systems
• Are viruses living organisms?
– Maybe
• The origins of molecular biology lie in early studies of
viruses that infect bacteria
T4 bacteriophage attacking E. coli
• Bacteria are
prokaryotes with
cells much smaller
and more simply
organized than
those of
eukaryotes
• Viruses are
smaller and
simpler than
bacteria
Virus
Bacterium
Animal
cell
Animal cell nucleus
0.25 µm
Viruses
• Viruses were detected indirectly long before they were actually seen
• Tobacco mosaic disease stunts growth of tobacco plants and gives
their leaves a mosaic coloration
• In the late 1800s, researchers hypothesized that a particle smaller than
bacteria caused the disease
• In 1935, this hypothesis was confirmed by
crystallizing the infectious particle, tobacco mosaic virus (TMV)
Structure of Viruses
•
Viruses are not cells
•
Viruses are very small infectious particles consisting of
nucleic acid enclosed in a protein coat and,
in some cases, a membranous envelope
•
Viral genomes may consist of:
1. Double- or single-stranded DNA
2. Double- or single-stranded RNA
Depending on its type of nucleic acid,
a virus is called a DNA virus or an RNA virus
Capsomere
RNA
DNA
Membranous
RNA
envelope
Capsid
Head
DNA
Tail
sheath
Capsomere
of capsid
Tail
fiber
Glycoprotein
18  250 nm
20 nm
(a) Tobacco
mosaic virus
Glycoproteins
70–90 nm (diameter) 80–200 nm (diameter)
50 nm
(b) Adenoviruses
80  225 nm
50 nm
50 nm
(c) Influenza viruses (d) Bacteriophage T4
RNA
DNA
Capsomere
capsidis the protein shell that
encloses the viral genome;
Capsomere each protein subunit is a
of capsid
capsomere
18 x 250 nm
20 nm
(a) Tobacco mosaic
virus
Glycoprotein
70–90 nm (diameter)
50 nm
(b) Adenoviruses
• Some viruses have
membranous envelopes
that help them infect hosts
– surround the capsids of
influenza viruses and many
other viruses found in
animals
Membranous
envelope
RNA
Capsid
Glycoproteins
80–200 nm (diameter)
– are derived from the
host cell’s membrane,
contain a combination of
viral and host cell molecules
50 nm
(c) Influenza viruses
•
•
Bacteriophages,
also called phages,
are viruses that infect bacteria
They have:
– the most complex capsids
found among viruses
– an elongated capsid head
that encloses their DNA
Head
DNA
Tail
sheath
Tail
fiber
80 x 225 nm
– a protein tailpiece that
attaches the phage to the
host and injects the phage
DNA inside
50 nm
(d) Bacteriophage T4
Viral
Replicative Cycle
•
•
Viruses are obligate
intracellular parasites,
which means they can
reproduce only within a host cell
Each virus has a host range,
a limited number of host cells
that it can infect
•
Once a viral genome has
entered a cell, the cell begins to
manufacture viral proteins
•
The virus makes use of
host enzymes, ribosomes,
tRNAs, amino acids, ATP, and
other molecules
Entry into cell and
uncoating of DNA
VIRUS
DNA
Capsid
Transcription
Replication
HOST CELL
host enzymes
replicate the Viral DNA
viral genome
mRNA
Viral DNA
Capsid
proteins
Self-assembly of
new virus particles
and their exit from cell
Reproductive Cycles of Phages
• Phages are the best understood of all viruses
• Bacteria have defenses against phages, including restriction enzymes
that recognize and cut up certain phage DNA
• Phages have two reproductive mechanisms:
1. the lytic cycle
2. the lysogenic cycle
1 Attachment
The Lytic Cycle
culminates in the
death of the host cell
5 Release
2 Entry of phage
DNA and
degradation of
host DNA
digests the
host’s cell wall
Phage assembly
produces
new phages
4 Assembly
3 Synthesis of viral
genomes and
proteins
Head
Tail Tail fibers
•
A phage that reproduces only by the lytic cycle
is called a virulent phage
The Lysogenic Cycle
•
The lysogenic cycle replicates the phage genome without destroying the host
•
The viral DNA molecule is incorporated by genetic recombination into the
host cell’s chromosome; this integrated viral DNA is known as a prophage
Phage
DNA
Daughter cell
with prophage
The phage attaches to a
host cell and injects its DNA.
Many cell divisions
produce a large
population of
bacteria infected with
the prophage.
Phage DNA
circularizes
Phage
Bacterial
chromosome
Lytic cycle
The cell lyses, releasing phages.
Occasionally, a prophage
exits the bacterial chromosome,
initiating a lytic cycle.
Lysogenic cycle
Certain factors
determine whether
Lytic cycle or Lysogenic cycle
is induced
is entered
New phage DNA and proteins are
synthesized and assembled into phages.
The bacterium reproduces
normally, copying the prophage
and transmitting it to daughter cells.
Prophage
Phage DNA integrates into the bacterial
chromosomes, becoming a prophage.
temperate
phage
Phage
DNA
The phage attaches to a
host cell and injects its DNA.
Bacterial
chromosome
Prophage
Lysogenic cycle
Lytic cycle
• Virulent or temperate phage
• Temperate phage only
• Destruction of host DNA
• Genome integrates into bacterial
• Production of new phages
chromosome as prophage, which
• Lysis of host cell causes release
(1) is replicated and passed on to
of progeny phages
daughter cells and
(2) can be induced to leave the chromosome and initiate a lytic cycle
Two key variables in
classifying viruses that
infect animals:
– DNA or RNA
– single-stranded (ss)
double-stranded (ds)
http://en.wikipedia.org/wiki/Baltimore_classification
DNA
HPV
RNA
Retroviruses
•
The broadest variety of RNA genomes is found in viruses
that infect animals
•
Retrovirusesuse reverse transcriptase to copy their RNA genome into DNA
•
Human immunodeficiency virus (HIV)
is the retrovirus that causes
acquired immunodeficiency syndrome (AIDS)
Class VI. ssRNA; template for DNA synthesis
The viral DNA that is
integrated into the host
genome is called a
provirus
HIV
Membrane of
white blood cell
HOST CELL
Unlike a prophage,
a provirus remains a
permanent resident of
the host cell
reverse transcriptasecatalyzes the synthesis
of a DNA strand
complementary to the
viral RNA and a
second DNA strand
complementary to the 1st
Viral RNA
0.25 µm
HIV entering a cell
RNA-DNA
hybrid
DNA
NUCLEUS
Provirus
The host’s RNA
polymerase transcribes the
proviral DNA into RNA
molecules
Chromosomal
DNA
RNA genome
for the
next viral
generation
The RNA molecules
function both as mRNA for
synthesis of viral proteins
and as genomes for new
virus particles released from
the cell
New HIV leaving a cell
mRNA
Viral Disease
• Diseases caused by viral infections affect
humans, agricultural crops, & livestock worldwide
• Viruses may damage or kill cells by causing the
release of hydrolytic enzymes from lysosomes
• Some viruses cause infected cells to produce
toxins that lead to disease symptoms
• Smaller, less complex entities called
viroids and prions
also cause disease in plants and animals
Vaccines
• vaccinesare harmless derivatives of pathogenic microbes that stimulate the
immune system to mount defenses against the actual pathogen
– can prevent certain viral illnesses
•
•
•
•
•
Hepatitis B, A
Polio (IPV)
Rotavirus
MMRV- Measles, Mumps, Rubella, Varicella (chicken pox)
HPV
Other crucial childhood vaccines that protect against bacteria:
 DTaP (Diptheria, Tetanus, Pertussis [whooping cough])
 Hib (Haemophilus influenzae type b)
 Pneumococcal
Viral infections cannot be treated by antibiotics
antiviral drugscan help to treat, though not cure,
viral infections by interfering with viral replication
HIV can be treated
with the drug AZT.
AZT has a 100- to 300-fold greater affinity
for the HIV reverse transcriptase, as compared to
the human DNA polymerase
http://en.wikipedia.org/wiki/Zidovudine