Chapter 6
An Introduction
to Viruses
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The Search for the Elusive Virus
• Louis Pasteur postulated that rabies was
caused by a virus (1884)
• Ivanovski and Beijerinck showed a disease in
tobacco was caused by a virus (1890s)
• 1950s virology was a multifaceted discipline
– Viruses: noncellular particles with a definite
size, shape, and chemical composition
2
The Position of Viruses in the
Biological Spectrum
• There is no universal
agreement on how and
when viruses originated
• Viruses are considered
the most abundant
microbes on earth
• Viruses played a role in
the evolution of Bacteria,
Archaea, and Eukarya
• Viruses are obligate
intracellular parasites
3
General Size of Viruses
• Size range – most <0.2 μm; requires electron
microscope
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BACTERIAL CELLS
Rickettsia
0.3 mm
Viruses
1. Poxvirus
2. Herpes simplex
3. Rabies
4. HIV
5. Influenza
6. Adenovirus
7. T2 bacteriophage
8. Poliomyelitis
9. Yellow fever
Streptococcus
1 mm
(1)
(2)
Protein Molecule
10. Hemoglobin
molecule
250 nm
150 nm
125 nm
110 nm
100 nm
75 nm
65 nm
30 nm
22 nm
E. coli
2 mm long
(10)
(9)
(8)
15 nm
(7)
(3)
(6)
(4)
(5)
4
YEAST CELL – 7 mm
Viral Structure
• Viruses bear no resemblance to cells
– Lack protein-synthesizing machinery
• Viruses contain only the parts needed to invade
and control a host cell
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Capsid
Covering
Envelope (not
found in all viruses)
Virus
particle
Nucleic acid molecule(s)
(DNA or RNA)
Central core
Matrix proteins
Enzymes (not found in
all viruses)
5
General Structure of Viruses
• Capsids
– All viruses have capsids
(protein coats that
enclose and protect their
nucleic acid)
– The capsid together with
the nucleic acid is the
nucleocapsid
– Some viruses have an
external covering called
an envelope; those
lacking an envelope are
naked
– Each capsid is made of
identical protein subunits
called capsomers
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Capsid
Nucleic acid
(a) Naked Nucleocapsid Virus
Envelope
Spike
Capsid
Nucleic acid
6
(b) Enveloped Virus
General Structure of Viruses
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• Two structural
capsid types:
– Helical continuous helix
of capsomers
forming a
cylindrical
nucleocapsid
Discs
Nucleic acid
Capsomers
(a)
(b)
Nucleic acid
Capsid begins
forming helix.
(c)
7
General Structure of Viruses
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• Two structural
capsid types:
– Icosahedral –
20-sided figure
with 12 evenly
spaced corners
– Ex: adenovirus
(a) Capsomers
Facet
Capsomers
Vertex
Nucleic
acid
(b)
Capsomers
Vertex
Fiber
(c)
8
(d) © Dr. Linda Stannard, UCT/Photo Researchers, Inc.
General Structure of Viruses
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• Viral envelope
– Mostly animal viruses
– Acquired when the
virus leaves the host
cell
– Exposed proteins on
the outside of the
envelope, called
spikes, are essential
for attachment of the
virus to the host cell
Capsid
Nucleocapsid
Nucleic acid
© Dennis Kunkel/CNRI/Phototake
(b)
(a)
Hemagglutinin spike
Neuraminidase spike
Matrix protein
Lipid bilayer
Nucleocapsid
(c)
50 nm
Spikes
Nucleocapsid
9
(d)
Dr. F. A. Murphy/CDC
Functions of Capsid/Envelope
• Protects the nucleic acid
when the virus is outside
of the host cell
• Helps the virus bind to a
cell surface and assists
the penetration of the
viral DNA or RNA into a
suitable host cell
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Capsomers
© Dr. Linda Stannard, UCT/Photo Researchers, Inc.
Fred P. Williams, Jr./EPA
(a)
Envelope Capsid DNA core
• Stimulate the immune
system to produce
antibodies to neutralize
the virus
10
(b)
© Eye of Science/Photo Researchers, Inc.
General Structure of Viruses
• Complex viruses: atypical viruses
– Poxviruses lack a typical capsid and are covered by a
dense layer of lipoproteins
– Some bacteriophages have a polyhedral nucleocapsid
along with a helical tail and attachment fibers
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240 – 300 nm
Nucleic acid
Core
membrane
Nucleic acid
(a)
Capsid head
Collar
200 nm
Outer
envelope
Soluble
protein
antigens
Sheath
Lateral body
Tail
fibers
Tail
pins
Base plate
(c)
11
(b)
© Bin Ni, Chisholm Lab, MIT
Types of Viruses
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A. Complex Viruses
B. Enveloped Viruses
Helical
Icosahedral
(1)
(3)
(5)
(2)
(4)
(6)
C. Nonenveloped Naked Viruses
Helical
Icosahedral
(8)
(7)
(9)
A. Complex viruses:
(1) poxvirus, a large DNA virus
(2) flexible-tailed bacteriophage
B. Enveloped viruses:
With a helical nucleocapsid:
(3) mumps virus
(4) rhabdovirus
With an icosahedral nucleocapsid:
(5) herpesvirus
(6) HIV (AIDS)
C. Naked viruses:
Helical capsid:
(7) plum poxvirus
Icosahedral capsid:
(8) poliovirus
(9) papillomavirus
12
Concept Check:
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How would you describe this virus?
A. Icosahedral and Naked
B. Helical and Naked
C. Complex and Naked
D. Icosahedral and Enveloped
E. Helical and Enveloped
F. Complex and Enveloped
© Dennis Kunkel/CNRI/Phototake
Nucleic Acids
• Viral genome – either DNA or RNA but never
both
• Carries genes necessary to invade host cell and
redirect cell’s activity to make new viruses
• Number of genes varies for each type of virus –
few to hundreds
14
Nucleic Acids
• DNA viruses
– Usually double stranded (ds) but may be single
stranded (ss)
– Circular or linear
• RNA viruses
– Usually single stranded, may be double stranded, may
be segmented into separate RNA pieces
– ssRNA genomes ready for immediate translation are
positive-sense RNA
– ssRNA genomes that must be converted into proper
form are negative-sense RNA
15
General Structure
• Pre-formed enzymes may be present
– Polymerases – synthesize DNA or RNA
– Replicases – copy RNA
– Reverse transcriptase – synthesis of DNA
from RNA (AIDS virus)
16
How Viruses Are Classified
• Main criteria presently used are structure, chemical
composition, and genetic makeup
• Currently recognized: 3 orders, 63 families, and 263
genera of viruses
• Family name ends in -viridae, i.e.Herpesviridae
• Genus name ends in -virus, Simplexvirus
• Common name: Herpes simplex virus I (HSV-I)
17
Human Viruses & Viral Diseases
18
19
Modes of Viral Multiplication
General phases in animal virus multiplication cycle:
1. Adsorption – binding of virus to specific molecules on
the host cell
2. Penetration – genome enters the host cell
3. Uncoating – the viral nucleic acid is released from the
capsid
4. Synthesis – viral components are produced
5. Assembly – new viral particles are constructed
6. Release – assembled viruses are released by
budding (exocytosis) or cell lysis
20
Adsorption and Host Range
• Virus coincidentally collides with a susceptible host cell and
adsorbs specifically to receptor sites on the membrane
• Spectrum of cells a virus can infect – host range
– Hepatitis B – human liver cells of humans
– Poliovirus – primate intestinal and nerve cells of primates
– Rabies – various cells of many mammals
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Envelope spike
Host cell membrane
Capsid spike
Receptor
Host cell
membrane
Receptor
21
(a)
(b)
Penetration/Uncoating
• Flexible cell membrane is penetrated by the
whole virus or its nucleic acid by:
– Endocytosis – entire virus is engulfed and
enclosed in a vacuole or vesicle
• Both enveloped and naked viruses
– Fusion – envelope merges directly with
the host membrane resulting in
nucleocapsid’s entry into cytoplasm
• Only in enveloped viruses
22
Variety in Penetration and Uncoating
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Host cell
membrane
Free
RNA
Receptors
Uncoating of
nucleic acid
Receptor-spike
complex
Membrane
fusion
Irreversible
attachment
(a)
Entry of
nucleocapsid
Uncoating step
Host cell membrane
Virus in
vesicle
Specific
attachment
(b)
Vesicle, envelope and
capsid break down
Free
DNA
Engulfment
Capsid
RNA
Nucleic
acid
23
Receptor
(c)
Adhesion of virus to host receptors
Engulfment into vesicle
Viral RNA is released from vesicle
Replication and Protein Production
• Varies depending on whether the virus is a
DNA or RNA virus
• DNA viruses generally are replicated and
assembled in the nucleus
• RNA viruses generally are replicated and
assembled in the cytoplasm
– Positive-sense RNA contain the message for
translation
– Negative-sense RNA must be converted into
positive-sense message
24
Release
• Assembled viruses leave the host
cell in one of two ways:
– Budding – exocytosis;
nucleocapsid binds to membrane
which pinches off and sheds the
viruses gradually; cell is not
immediately destroyed
– Lysis – nonenveloped and
complex viruses released when
cell dies and ruptures
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(b)
© Chris Bjornberg/Photo Researchers, Inc.
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Host cell membrane
Viral nucleocapsid
Viral glycoprotein spikes
Cytoplasm
Capsid
RNA
Budding
virion
(a)
Viral matrix
protein
Free infectious
virion with envelope
25
Animal Virus Multiplication
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Penetration. The virus is engulfed
into a vesicle and its envelope is
Uncoated, thereby freeing the viral
RNA into the cell cytoplasm.
Synthesis: Replication and Protein Production.
Under the control of viral genes, the cell
synthesizes the basic components of new viruses:
RNA molecules, capsomers, spikes.
Assembly. Viral spike
proteins are inserted into the
cell membrane for the viral
envelope; nucleocapsid is
formed from RNA and
capsomers.
Release. Enveloped viruses bud off
of the membrane, carrying away an
envelope with the spikes. This
complete virus or virion is ready to
infect another cell.
26
Concept Check:
Viruses commonly contain both DNA and RNA.
A. True
B. False
Damage to Host Cell
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Cytopathic effects - virusinduced damage to cells
1. Changes in size and shape
2. Cytoplasmic inclusion
bodies
3. Inclusion bodies
4. Cells fuse to form
multinucleated cells
5. Cell lysis
6. Alter DNA
7. Transform cells into
cancerous cells
Multiple
nuclei
Normal
cell
Giant cell
CDC
(a)
CDC
Inclusion bodies
28
(b)
© Massimo Battaglia, INeMM CNR, Rome Italy
Effects of Some Human Viruses
29
Persistent Infections
• Persistent infections - cell harbors the virus and
is not immediately lysed
• Can last weeks or host’s lifetime
• Activate causing recurrent symptoms
• Several virus remain in latent state – they are
inactive over long periods
– Measles virus – may remain hidden in brain cells for
many years
– Herpes simplex virus – cold sores and genital herpes
– Herpes zoster virus – chickenpox and shingles
30
Viral Damage
• Some animal viruses enter the host cell and
permanently alter its genetic material resulting in
cancer, these viruses are termed oncogenic
• The cause transformation of the cell
• Transformed cells have an increased rate of
growth, alterations in chromosomes, and the
capacity to divide for indefinite time periods
resulting in tumors
• Mammalian viruses capable of initiating tumors
are called oncoviruses
– Papillomavirus – cervical cancer
– Epstein-Barr virus – Burkitt’s lymphoma
31
Multiplication Cycle in Bacteriophages
• Bacteriophages – bacterial viruses (phages)
• Most widely studied are those that infect
Escherichia coli – complex structure, DNA
• Multiplication goes through similar stages as
animal viruses
• Only the nucleic acid enters the cytoplasm uncoating is not necessary
• Release is a result of cell lysis induced by
viral enzymes and accumulation of viruses lytic cycle
32
Steps in Phage Replication
1. Adsorption – binding of virus to specific
molecules on host cell
2. Penetration – genome enters host cell
3. Replication – viral components are produced
4. Assembly – viral components are assembled
5. Maturation – completion of viral formation
6. Lysis & Release – viruses leave the cell to
infect other cells
33
Lysogeny: The Silent Virus Infection
• Not all phages complete the lytic cycle
• Some DNA phages, called temperate phages, undergo
adsorption and penetration but don’t replicate
• The viral genome inserts into bacterial genome and
becomes an inactive prophage – the cell is not lysed
• Prophage is retained and copied during normal cell
division resulting in the transfer of temperate phage
genome to all host cell progeny – lysogeny
• Induction can occur resulting in activation of lysogenic
prophage followed by viral replication and cell lysis
34
Lysogeny
• Lysogeny results in the spread of the virus
without killing the host cell
• Phage genes in the bacterial chromosome can
cause the production of toxins or enzymes that
cause pathology
– Lysogenic conversion – bacterium acquires genes
from its phage
• Corynebacterium diphtheriae
• Vibrio cholerae
• Clostridium botulinum
35
Lytic and Lysogenic Lifecycles
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E. coli host
7 Release of viruses
Bacteriophage
Bacterial
DNA
Lysogenic State
Viral
DNA
1
2
Viral DNA becomes
latent as prophage.
Adsorption
6
Penetration
Lysis of weakened cell
Lytic
Cycle
DNA
splits
Spliced
viral
genome
3
Viral
DNA
5
Duplication of phage
components; replication of
virus genetic material
Maturation
Bacterial
DNA molecule
Capsid
The lysogenic state in bacteria.
The viral DNA molecule is inserted at
specific sites on the bacterial
chromosome. The viral DNA is
duplicated along with the regular
genome and can provide adaptive
genes for the host bacterium.
Tail
4
Assembly of
new virions
DNA
+
Tail fibers
Sheath
Bacteriophage
Bacteriophage assembly line.
First the capsomers are synthesized by the host
cell. A strand of viral nucleic acid is inserted
during capsid formation. In final assembly, the
prefabricated components fit together into whole
parts and finally into the finished viruses.
36
Comparison of Bacteriophage and Animal Virus
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Head
Bacterial
cell wall
Tube
Viral nucleic acid
Cytoplasm
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37
© K.G. Murti/Visuals Unlimited
Concept Check:
Which of the following is a step found in animal virus
multiplication but not in bacteriophage replication?
A. Adsorption
B. Penetration
C. Uncoating
D. Assembly
E. Release
Techniques in Cultivating and
Identifying Animal Viruses
• Obligate intracellular parasites that require
appropriate cells to replicate
• Methods used:
– Cell (tissue) cultures – cultured cells grow in sheets that
support viral replication and permit observation for
cytopathic effects
– Bird embryos – incubating egg is an ideal system; virus
is injected through the shell
– Live animal inoculation – occasionally used when
necessary
39
Methods for Growing Viruses
Inoculation
of embryo
Inoculation
of amniotic cavity
Air sac
Inoculation of
chorioallantoic
membrane
Amnion
Shell
Allantoic
cavity
Inoculation of
yolk sac
Albumin
40
(b)
Medical Importance of Viruses
• Viruses are the most common cause of acute
infections
• Several billion viral infections per year
• Some viruses have high mortality rates
• Viruses are major participants in the earth’s
ecosystem
41
Detection and Treatment of
Animal Viral Infections
• More difficult than other agents
• Consider overall clinical picture
• Take appropriate sample
– Infect cell culture – look for characteristic
cytopathic effects
– Screen for parts of the virus
– Screen for immune response to virus (antibodies)
• Antiviral drugs can cause serious side effects
42
Prions and Other Nonviral
Infectious Particles
Prions - misfolded proteins, contain no nucleic acid
– Extremely resistant to usual sterilization
techniques
– Cause transmissible spongiform
encephalopathies – fatal neurodegenerative
diseases
43
Prions Diseases
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Common in animals:
• Scrapie in sheep
and goats
• Bovine
spongiform
encephalopathies
(BSE), a.k.a. mad
cow disease
• Wasting disease in
elk
• Humans –
Creutzfeldt-Jakob
Syndrome (CJS)
Brain cell
Prion fibrils
© James King-Holmes/Institute of Animal Health/Photo Researchers, Inc.
(a)
44
Dr. Art Davis/CDC
(b)
Other Noncellular Infectious Agents
•
Satellite viruses – dependent on other viruses
for replication
– Adeno-associated virus – replicates only in cells
infected with adenovirus
– Delta agent – naked strand of RNA expressed only
in the presence of hepatitis B virus
•
Viroids – short pieces of RNA, no protein coat;
only been identified in plants
45