Download The Discovery and Structure of Viruses

6
Viruses
At the Threshold of Life
The Nature of Viruses
• Not really alive
• Not really completely inert
• Existence somewhere between living objects and
chemical compounds
The Discovery and Structure of Viruses
• The development of virology
– 1892 Dmitri Iwanoski
• Tobacco mosaic virus (TMV)
• Bacteria-free filtrate still infectious
• 1898 Martinus Beijerinck supported
these data
– 1930s Wendell Stanley
• Crystals of TMV indicated chemical
molecule
• Body responses indicated infectious
microbes
• The debate continued…
– 1933 Ernst Ruska
• Invention of electron microscope
• Finally allowed visualization of viruses
© National Library of Medicine
Figure 6.1a: The Russian pathologist Dmitri Iwanowski
The Discovery and Structure of Viruses
• The structure of viruses
– Size
• As small as 27 nm (0.027
mM); poliovirus
• At least as large as 250 nm
(0.25 mM); smallpox
• At least 500 could fit inside
single bacterium!
The Discovery and Structure of Viruses
• The structure of viruses
– Symmetry
• Helix
• Icosahedron
• Complex
The Discovery and Structure of Viruses
The Discovery and Structure of Viruses
• The components of viruses
– Minimum of nucleic acid and
protein = naked
– Some have an outer envelope
– Nucleic acid
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Called the “Genome”
RNA or DNA, not both
Segmented or non-segmented
Circular or linear
Single-stranded or double-stranded
Fig. 6.4a: naked Icosahedral virus
– Protein
• Capsid
• Capsomeres
– Nucelocapsid = genome + capsid
Fig. 6.4b: A naked helical virus
The Discovery and Structure of Viruses
• The components of
viruses
– Envelope
• Lipids
• Spikes
– No cytoplasm
– No metabolism
– No increase or
decrease in size
Fig. 6.4 Icosahedral and helical viruses
Figure 6.COinsert: A TEM of the ultra structural details of a number of
influenza virus particles, or “virions”
Courtesy of Dr. F.A. Murphy/CDC
Viral Replication: Lytic Cycle
Viral Replication
• Viral replication and disease
– Destruction of healthy cells
– EXAMPLES
• 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
Viral Replication
• Defense against viruses
– Immune system
• Antibodies: protein molecules made by B cells in the immune system,
in response to the presence of a virus.
• T cells: attack infected cells
– Antiviral drugs
• Acyclovir
• Amantadine
• Azidothymidine (AZT)
– Interferons: produced by cells when attacked (about 20)
Viral Replication
• Viral vaccines
– Stimulation of immune response without risking pathogenic
infection
– Inactivated
• Chemically destroyed virus genome, capsid intact
• Example: Salk polio vaccine
– Attenuated
• Live, but weakened virus
• Example: Sabin polio vaccine, chickenpox, MMR
– Genetically engineered
• Production of viral proteins by recombinant organism
• Example: Hepatitis B vaccine
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 equivalent is
retrovirus, HIV
• Typical for many
plant viruses
Figure 6.9: The formation of a provirus
Viral Replication
• Viroids and prions
– Viroids
• Single-stranded RNA
• No capsid
• Infect plants
– Prions
Proteinaceous infectious particles
No nucleic acid
Cause mad cow disease
Normal cellular protein
Change in conformation creates Prion
Results in spongiform
encephalopathy
© Ulf Sirborn/AP Photos
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Figure 6.11a: Stanley Prusiner,
winner of 1997 Nobel in
Physiology or Medicine for his
work on prions as agents of
infectious disease
Viruses and Cancer
• The development of cancer
– Cancer
• Uncontrolled mitotic reproduction of cells
• Faster replication than normal cells
• Result is mass of cells called tumor
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Benign tumors
Malignant tumors
Oncology
Dedifferentiation
Loss of contact inhibition
Modes of disease
Viruses and Cancer
• The involvement of viruses
– Carcinogens
– Some viruses can induce tumors
– Examples
• Epstein-Barr virus
• Human T cell leukemia viruses (HTLVs)
• How viruses transform cells
– Michael Bishop and Harold Varmus
• Oncogenes
• Proto-oncogenes
• How viruses may turn proto-oncogenes into oncogenes
Viruses and Cancer: How Viruses Transform
Cells
Figure 6.12: The oncogene theory