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Chapter 13:
Viruses
Viruses
• Obligate intracellular parasites
─ Must use host cell’s machinery to replicate
• Viruses contain nucleic acid (DNA or RNA)
─ DNA or RNA can be single- or double-stranded
─ Surrounded by a protein coat (capsid)
• Some are enclosed by an envelope
Figure 13.2
Figure 13.1
Viruses:
Host Range
• Most viruses infect only specific types of cells in one
host species
─ Bacteriophages only infect certain bacteria
─ HIV only infects certain human leukocytes
• Host range: the spectrum of organisms or cells that a
given virus can infect
─ Determined by specific host cell attachment sites and
cellular factors
─ First step in a successful infection: virus attachment to
host cell
◦ Relies on chemical interactions between host cell and
virus
Viruses:
Structure
• Virion: fully developed infectious virus particle
─ i.e. nucleic acid in protein coat
• Protein coat: protects viral genome from environment and acts as
a vehicle for transmission
─ Capsid: protein coat
─ Capsomeres: protein coat subunits
◦ Type and arrangement specific to virus
Figure 13.2
Viruses:
Structure
Figure 13.4a, b
Complex Viruses
Figure 13.5a
Viruses:
Structure
• Some viruses have an envelope covering the capsid
─ May include spikes (carbohydrate-protein complexes)
◦ Helps in attachment to host cells
◦ Spikes are antigenic in animals
Figure 13.3
Viral Taxonomy
• Viral species: A group of viruses sharing the same
genetic information and ecological niche (host range)
─ Common names are used for species
─ Subspecies are designated by a number
Species:
Human herpes virus-1, HHV 2, HHV 3
Viral Multiplication
• Virions contain:
─ Genes for synthesis of new virions
─ A few (if any) enzymes it needs for early infection steps
─ Main concern: its own replication
• Everything else is supplied by the host cell (polymerases,
ribosomes, ATP, tRNA, etc.)
• Bacteriophages: two alternative mechanisms for
replication
─ Lytic cycle: Ends with lysis and death of host cell
─ Lysogenic cycle: Host cell lives with integrated viral
DNA (i.e. recombinant DNA)
Multiplication of Bacteriophages
(Lytic Cycle)
1. Attachment Phage attaches by tail fibers to
host cell (weak bonding)
2. Penetration Phage lysozyme opens cell wall,
tail sheath contracts to inject the
NA into cell
3. Biosynthesis Host cellular processes are halted;
Production of phage NA
and proteins takes over
4. Maturation
Assembly of phage particlesvirions
5. Release
Phage lysozyme breaks cell wall, virions
released to infect other bacteria
Figure 13.5a
Lytic Cycle
Bacterial
cell wall
Bacterial
chromosome
Capsid
DNA
Capsid
1 Attachment
Sheath
Tail fiber
2 Penetration
Base plate
Pin
Cell wall
Tail
Plasma membrane
Sheath contracted
3 Biosynthesis
-synthesis of viral
components
- Host cell DNA is
degraded
Tail core
Figure 13.11
Lytic Cycle, cont.
4 Maturation
-Virions assembled
Tail
DNA
What else can
happen here?
Capsid
5 Release
-Host cell lysis
Tail fibers
Figure 13.11
Multiplication of Bacteriophages:
Lysogenic Cycle
• Certain phages are capable of “choosing” between a
lytic cycle and a lysogenic cycle
• Lysogenic cycle: Prophage DNA stably incorporated in
host DNA
─ Prophage: phage DNA inserted into the host cell’s
chromosome
─ Virus does not immediately take the cell hostage; it
patiently hides and waits for a signal (UV, chemical)
◦ Prophage genes are repressed by phage-derived
repressor proteins that bind to prophage operators
The Lysogenic Cycle
Figure 13.12
Consequences of Lysogeny
• Phage conversion of the host cell: the host cell
obtains new properties due to the presence of the
prophage
─ Some toxins are carried by prophages: botulinum,
scarlet fever, cholera
• Specialized transduction
Specialized Transduction
Prophage
gal gene
Bacterial DNA
1 Prophage exists in galactose-using host
(containing the gal gene).
Galactose-positive
donor cell
gal gene
2 Phage genome excises, carrying
with it the adjacent gal gene from
the host.
gal gene
3 Phage matures and cell lyses, releasing
phage carrying gal gene.
4 Phage infects a cell that cannot utilize
galactose (lacking gal gene).
Galactose-negative
recipient cell
5 Along with the prophage, the bacterial gal
gene becomes integrated into the new
host’s DNA.
6 Lysogenic cell can now metabolize
galactose.
Galactose-positive recombinant cell
Figure 13.13
Multiplication of Animal Viruses
Attachment
Entry
Uncoating
Bacteriophages
Tail fibers attach to cell
wall proteins
Viral DNA injected into
cell
Not required
Biosynthesis In cytoplasm
(Chronic
Lysogeny
infection)
Release
Host cell lysed
Animal viruses
Attachment sites:
plasma membrane
proteins
Capsid enters cell
Enzymatic removal of
capsid proteins
In nucleus or cytoplasm
Latency
Budding from PM or
rupture of PM
Table 13.3
Release of an enveloped virus by
budding
(envelope proteins)
Figure 13.20
Influenza
• Viral infection of the lower respiratory system
• Chills, fever, headache, muscle aches
─ 50,000-70,000 flu deaths in the US per year
• Strains classified by H and N antigens (spikes)
Influenza
• Hemagglutinin (H) spikes:
attachment to host cells
─ H1-15
• Neuraminidase (N) spikes:
to release virus from cell
─ N1-9
• Both used for identifying
viral strains and vaccine
production
Figure 24.16
Influenza:
Why aren’t we immune?
• Antigenic drift:
─ Mutations in genes encoding H or N spikes
◦ Influenza (RNA virus) has a high mutation rate
─ Minor variations; may involve only 1 amino acid change
─ Allows virus to avoid immune recognition developed
from previous infections
◦ Vaccines change each year
• Antigenic shift
─ Major changes in H and N spikes
─ Probably due to genetic recombination between
different strains infecting the same cell
Influenza
• Spanish flu of 1918
─ This strain acquired a lethal mutation
◦ Mortality rate over 20X that of previous flu epidemics
─ Killed nearly 50 million people worldwide
◦ Killed at least 700,000 in the US
◦ WWI-related transportation likely aided its spread
─ Young adults had the highest susceptibility
─ Virus was able to infect lungs and cause viral
pneumonia
─ Sequencing of this virus in 2005 determined the virus
arose from an avian virus with 10 amino acid changes
that led to the lethal phenotype
“Some 1,600 persons died in Seattle
during the next six months despite
the closing of theaters and schools,
the banning of public gatherings,
and the widespread wearing of
gauze masks.”
http://www.historylink.org/db_images/Spokane_Knoll_1918.JPG
Influenza
• Influenza strain H5N1: Avian flu
─ Some birdhuman transmission at large bird farms in
SE Asia
◦ 6 people died in 1997
─ Major concern: this flu strain may develop mutations
that allow human-to-human transmission
◦ A purely avian virus “looks” foreign to humans
−i.e. We don’t have immunity
◦ Previous pandemic episodes involved the emergence
of a completely new strain
Influenza
• Flu vaccines
─ Typically directed at three
most prominent strains in
circulation at the time of
development
◦ New antigens must be
identified by February
─ Vaccine production is slow
◦ Grown in egg embryos
Flu vaccine production
Vaccine manufacturers receive seed virus from CDC/FDA
Seed viruses are injected into chicken eggs
Several days
JanMay
Eggshell is broken; egg white collected to harvest viruses
Multiple purification steps
Chemical treatment to inactivate viruses
June/
July
FDA tests each manufacturer’s strains for purity and potency
Three different strains are blended
Aug.
Vaccines are packaged for distribution and refrigerated
Sept.
Shipping begins
Oct/
Nov
Vaccinations begin
Immunity takes about two weeks
Latent and Persistent Viral
Infections
• Latent Viral Infections
─ Virus remains in asymptomatic host cell for long
periods (analogous to lysogeny)
◦ Herpesviruses: Cold sores, shingles
• Persistent Viral Infections
─ Disease processes occur over a long period, generally
fatal
◦ Virions build up over a long period of time