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Transcript
Slide 1
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6
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Viruses
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At the Threshold of Life
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Slide 2
Looking Ahead
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• On completing this chapter, you should be able to:
– Explain the events leading to the discovery of viruses and
recognize some turning points in the development of virology;
– Appreciate the distinctive structure of viruses, including their
incredibly small size and relatively simple components;
– describe the stages and details of the replication process
exhibited by viruses;
– Explain the significance of viral replication with respect to the
disease process and the development of resistance to viral
disease;
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Slide 3
Looking Ahead
• On completing this chapter, you should be
able to:
– Identify some methods for controlling viruses and
for using viruses to benefit society;
– Recognize the existence of certain types of
subviral particles;
– Summarize the development of cancer and
understand the involvement of viruses in this
dreaded disease.
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Slide 4
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What is life
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• Is cellular
• Growth
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– Increase in numbers by reproducing
– Increase in size
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• Has metabolic processes
– Uses energy
– Excretes waste products
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• Can respond to its environment
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Slide 5
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The Nature of Viruses
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• Not really alive
– Lack the capacity to perform any of the life processes
on their own.
• Not really completely inert
– When in the presence of a target cell they will attach
and incorporate their DNA or RNA into the cells
function.
• Existence somewhere between living objects and
chemical compounds
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Slide 6
The Discovery and Structure of Viruses
• The development of virology
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– 1892 Dmitri Iwanoski
• Tobacco mosaic virus (TMV)
• Bacteria-free filtrate still infectious
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– Viruses were small enough to get
past the filter.
• 1898 Martinus Beijerinck supported
these data
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– 1930s Wendell Stanley
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• Crystals of TMV
– 1933 Ernst Ruska
• Invention of electron microscope
– Finally allowed visualization of viruses
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© National Library of Medicine
Dmitri Iwanowski
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Slide 7
The Discovery and Structure of Viruses
•
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The structure of viruses
– Size
• As small as 27 nm (0.027 mM); poliovirus
• Some as large as 250 nm (0.25 mM); smallpox
• At least 500 could fit inside single bacterium!
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Figure 6.2: Size
relationships among
microbes
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Slide 8
The Discovery and Structure of Viruses
• The structure of viruses
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– Symmetry
• Helix
• Icosahedron
• Complex
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Courtesy of Dr. Sara Miller, Duke University Medical Center.
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Fig. 6.5
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Slide 9
The Discovery and Structure of Viruses
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• The components of viruses
– Minimum of nucleic acid and
protein coat
– Nucleic acid
•
•
•
•
•
Genome
RNA or DNA, not both
Segmented or non-segmented
Circular or linear
Single-stranded or double-stranded
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Fig. 6.4a: naked Icosahedral virus
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– Protein
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• Capsid (a coat surrounding the
Nucleic acid)
– Made of Capsomeres
– Nucelocapsid: a combination of
the nucleic acide and the protein
capsid. This is a complete virus.
Fig. 6.4b: A naked helical virus
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Slide 10
The Discovery and Structure of Viruses
• The components of viruses
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– Some viruses have an Envelope
• Often made of Lipids taken from the
host cell
• Often contains surface spikes which
allow adhesion
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– No cytoplasm
– No metabolism
– No increase or decrease in size
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Fig. 6.4 Icosahedral and helical viruses
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Slide 11
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Viral Replication
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• The stages of replication
– Attachment
• Binding to receptor site on target cell
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– Penetration
• Fusion and entry of target cell
– Uncoating
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• Release of genome into cell
– Synthesis
• Program of viral gene expression
• Translation of viral proteins
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– Assembly
• Putting all newly synthesized parts together
– Release
• New viruses exit infected cell, leaving spent, dead cell behind
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Slide 12
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Viral Replication: Lytic Cycle
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Figure 6.7:
Replication
of a DNA
virus
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Slide 13
Viral Replication
• When viruses don’t
replicate
– Lysogeny
• Integration of viral
genome into host’s
genome
• Viral genome become
dormant
• Integrated viral genome
is known as provirus
• Human equivalents are
HIV, herpes,
• Typical for many plant
viruses
Figure 6.9: The formation of a provirus
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Slide 14
Viral Replication
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• Viral replication and disease
– Destruction of healthy cells
– Viral hepatitis
• Destruction of liver cells by infection
• Loss of liver function
– AIDS
• Destruction of immune cells
• Loss of immune control over other infectious agents
– Rabies
• Destruction of nerves
• Loss of control by nervous system
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Slide 15
Viral Replication
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• Defense against viruses
– Immune system
• Antibodies (bind to and block the virus)
• T cells (destroy cells infected with virus)
– Antiviral drugs
• Acyclovir
• Amantadine
• Azidothymidine (AZT)
– Interferons
• Released by infected cells this substance blocks the uptake of
viruses in healthy cells.
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Slide 16
Viral Replication
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• Viral vaccines
– Stimulation of immune response without risking pathogenic infection
– Inactivated
• Chemically destroyed virus
• Example: Salk polio vaccine
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– Attenuated
• Live, but weakened virus
• Example: Sabin polio vaccine
– Genetically engineered
• Production of viral proteins by recombinant organism
• Example: Hepatitis B vaccine
– Important part of combating bioterrorism
• Example. Those immunized against smallpox would be immune if smallpox
were used as a weapon.
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Slide 17
Viral Replication
• Viral cultivation
– Difficult because viruses require a living organism to
use its cellular processes.
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• 1930s: Claud Johnson and Ernest Goodpasture
– Growth of viruses in fertilized chicken eggs
• 1940s cell culture (living human or other cells grown on a
media)
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– Derived from dispersed tissues
• 1950s virus infection of cells in culture
– Vaccine production
• Diploid fibroblast cultures
• Continuous cell line cultures
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Slide 18
Viral Replication
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• Viruses as research tools
–
–
–
–
Discovery of ribosome, mRNA functions
Gene therapy delivery vehicles
Vaccine agents
Agricultural protection
• Viruses and evolution
– Presumed origin of viruses as normal cellular DNA or RNA
– Viruses as agents that drive evolution
• Incorporating viral DNA sometimes introduce a beneficial trait that
can be passed on.
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Slide 19
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Viral Replication
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• Viroids and prions
– Viroids
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• Single-stranded RNA
• No capsid
• Infect plants
– Prions
Stanley Prusiner
Proteinaceous infectious particles
No nucleic acid
Cause mad cow disease
PrPc is normal cellular protein
Change in conformation creates PrPsc
Results in spongiform
encephalopathy
© Ulf Sirborn/AP Photos
•
•
•
•
•
•
•
Figure 6.11a: Stanley Prusiner,
winner of 1997 Nobel in
Physiology or Medicine for his
work on prions as agents of
infectious disease
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Slide 20
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Viral Replication: Prions
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Courtesy of APHIS photo by Dr. Al Jenny/CDC
Figure 6.11b: A photomicrograph of brain tissue showing
vacuolar degeneration of gray matter characteristic of
human and animal prion diseases
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Slide 21
Viruses and Cancer
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• The development of cancer
– Cancer
•
•
•
•
Uncontrolled mitotic reproduction of cells
Faster replication than normal cells
Result is mass of cells called tumor
Some known forms caused by viruses
– Benign tumors (do not spread but that does not make them
harmless)
– Malignant tumors (those that spread)
– Oncology (the study of cancer)
– Dedifferentiation (cells lose their characteristics)
– Loss of contact inhibition (continue to grow)
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Slide 22
Viruses and Cancer
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• The involvement of viruses
– Carcinogens
– Some viruses can induce tumors
– Examples
• Epstein-Barr virus (Burkitts Lymphoma)
• Human T cell leukemia viruses (HTLVs)
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• How viruses transform cells
– Michael Bishop and Harold Varmus
• Oncogenes
• Proto-oncogenes
• How viruses may turn proto-oncogenes into oncogenes
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Slide 23
Viruses and Cancer: How Viruses
Transform Cells
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Figure 6.12: The oncogene theory
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Slide 24
Summary
•Know the definition of life and how a virus fits in.
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•Understand the structure of viruses
•Understand the mechanism and types of viral replication
•Understand the difficulties in culturing viruses
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•Know the ways viruses disrupt cell function
•How can viruses be used in research
•What roles might viruses play in evolution
•Describe a viroid and a prion
•How can viruses function in cancers
•Learn the related key terms in your text.
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