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Chapter 6

An Introduction
to Viruses

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Swine Flu Symptoms
If you wake up and look like this in the mirror,
…..
please don’t come to class
*
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
*
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

*
General Size of Viruses
• Size range – most <0.2 μm; requires electron
microscope
Copyright© The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

BACTERIAL
CELLS

Rickettsi
a
0.3 μm

Streptococc Viruse
(1) E. coli
us s
1. 250 nm
2 μm
1 μm 2. Herpes
Poxvirus 150 nm (10) long
3.
simplex 125 nm
4.
Rabies 110 nm
5.
HIV 100 nm (9)
6.
Influenza 75 nm
7. T2
Adenovirus 65 nm
(2) 8.
bacteriophage 30 nm (8)
9. Yellow
Poliomyelitis 22 nm
fever
Protein
Molecule
10. 15 nm
Hemoglobin (7)
molecule
(3)
(6)
(4) (5)

*
YEAST CELL – 7
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
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Capsi
d
Envelope (not
Coveri
found in all
ng
Virus viruses)
partic
le Nucleic acid
molecule(s)
Central (DNA or RNA)
core Matrix proteins
Enzymes (not *
found in
General Structure of Viruses
• Capsids Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

– All viruses have capsids


(protein coats that Capsi
d
enclose and protect their
nucleic acid) Nucleic
acid
– The capsid together with
the nucleic acid is the
nucleocapsid (a) Naked Nucleocapsid
Virus

– Some viruses have an Envelop


e
external covering called
Spik
an envelope; those e

lacking an envelope are Capsi


naked d

– Each capsid is made of Nucleic


acid
identical protein subunits *
called capsomers (b) Enveloped
Virus
General Structure of Viruses
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

• Two structural Disc


s
capsid types: Capsomer
Nucleic
acid
s
– Helical -
continuous helix (a

of capsomers )

forming a
cylindrical
nucleocapsid (b
)
– Icosahedral Nucleic
acid
Capsid
begins
forming
helix.

(c *
)
General Structure of Viruses
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

• Two structural (a)


Face

capsid types:
Capsomers
t
Capsomer
s

– Helical - Verte
x

– Icosahedral - Nuclei
c
acid

20-sided with 12 (b
)

corners
Capsomer
s

Verte
x
Fibe
r

(c
)

*
(d © Dr. Linda Stannard, UCT/Photo Researchers, Inc.
)
General Structure of Viruses
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

• Viral envelope
– Mostly animal viruses Capsi

– Acquired when the


d Nucleocap
sid

virus leaves the host


Nucleic
acid
© Dennis Kunkel/CNRI/Phototake

cell (a
)
(b
)
Hemagglutinin
spike

– Exposed proteins on Neuraminidase


spike

the outside of the Matrix

envelope, called
protein

Lipid

spikes, are essential


bilayer

for attachment of the


virus to the host cell (c 50
Nucleocapsi
d

) nm

Spike
s
Nucleocapsi
d

*
Dr. F. A. Murphy/CDC
(d
Functions of Capsid/Envelope
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

• Protects the nucleic acid


when the virus is outside
of the host cell

• Helps the virus bind to a


cell surface and assists Capsomer
© Dr. Linda Stannard, UCT/Photo Researchers, Inc.

the penetration of the Fred P. Williams, Jr./EPA


s
(a
)

viral DNA or RNA into a Envelop


e
Capsi DNA
d core

suitable host cell

*
© Eye of Science/Photo Researchers, Inc.
(b
)
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
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

240–300
nm
Nucleic
Core Capsid acid
membra head
ne 200 Colla
Nucleic
nm r
acid Sheat
Outer h
envelop
e Soluble
protein Tail
Lateral
antigen fiber
(a body
s s
)

Tail Base
pin plate
s
(c
)

*
(b © Bin Ni, Chisholm Lab, MIT
Types of Viruses
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

A. Complex B. Enveloped
Viruses Viruses
Helical Icosahedra
l

(1) (3) (5)

(2) (4) (6)

C. Nonenveloped Naked A. Complex viruses:


Viruses (1) poxvirus, a large DNA
Helical Icosahedra virus
l (2) flexible-tailed
B. Enveloped viruses:
bacteriophage
With a helical nucleocapsid:
(3) mumps virus
(4) rhabdovirus
With an icosahedral
nucleocapsid:
(8)
(5) herpesvirus
(6) HIV (AIDS)
C. Naked viruses:
Helical capsid:
(7) plum
poxvirus
Icosahedral
*
(7) (9) capsid:
(8) poliovirus
Concept Check:
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

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

*
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

*
General Structure
• Pre-formed enzymes may be present
– Polymerases – DNA or RNA
– Replicases – copy RNA
– Reverse transcriptase – synthesis of DNA
from RNA (AIDS virus)

*
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

• Herpes simplex virus I (HSV-I)

*
Human Viruses & Viral Diseases

*
*
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

*
Animal Virus Multiplication
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Host Cell
Cytoplasm
Receptors
Cell
membrane Spikes

1 Adsorption. The virus attaches to


its 1
host cell by specific binding of its
spikes to cell receptors.

2 Penetration. The virus is


engulfed
3 into a vesicle and its envelope is
Uncoated, thereby freeing the
2 viral
RNA into the cell cytoplasm.
3

Nucleus

4 Synthesis: Replication and Protein


RNA
Production.
Under the control of viral genes, the cell
synthesizes the basic components of new
viruses:
4 RNA molecules, capsomers, spikes.

New
spike
s

New
5 Assembly. Viral spike
capsomer
s proteins are inserted into
5 the
Ne cell membrane for the viral
w envelope; nucleocapsid is
RNA formed from RNA and
capsomers.

6 Release. Enveloped viruses bud


of 6
of the membrane, carrying away
an
envelope with the spikes. This
complete virus or virion is ready
*
to
infect another cell.
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
– Poliovirus – primate intestinal and nerve cells
– Rabies – various cells of many mammals
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Envelope
spikeHost cell
membrane Capsid
spike

Receptor

Host cell
membra
ne
Receptor

*
(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
– Fusion – envelope merges directly with
membrane resulting in nucleocapsid’s entry
into cytoplasm

*
Variety in Penetration and Uncoating
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Host cell Fre


membra e
ne
Recepto RNA
rs Uncoating
of
nucleic
Receptor- acid
Entry of
spike nucleocap
Irreversib Membrancomplex sid
(a le e
) attachme fusion
nt Uncoating
Host cell step
membrane

Fre
Virus Vesicle, envelope e
in and DN
Specific Engulfme vesicle capsid break down A
(b attachm nt
) ent

Capsi
d

RN
A
Nuclei
c
acid Recept *
or
(c Adhesion of virus to host Engulfment into Viral RNA is released from
receptors vesicle 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

*
Release
• Assembled viruses leave the host Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

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 (b
)
© Chris Bjornberg/Photo Researchers, Inc.

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Viral
Host cell
nucleocapsid
membrane Viral glycoprotein
spikes
Cytoplas
m
Capsi
d

RN
A

Buddin Free infectious


g virion with *
virion envelope
Viral
(a matrix
Concept Check:
Viruses commonly contain both DNA and RNA.

A. True
B. False
Damage to Host Cell Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Cytopathic effects - virus-


induced damage to cells
1. Changes in size and shape Norma
l
Multipl cell
2. Cytoplasmic inclusion e
nuclei

bodies
3. Inclusion bodies
Giant
4. Cells fuse to form cell

multinucleated cells
5. Cell lysis
CDC CDC
(a
) Inclusion
bodies
6. Alter DNA
7. Transform cells into
cancerous cells

*
© Massimo Battaglia, INeMM CNR, Rome Italy
(b
Effects of Some Human Viruses

*
Persistent Infections
• Persistent infections - cell harbors the virus and
is not immediately lysed
• Can last weeks or host’s lifetime; several can
periodically reactivate – chronic latent state
– 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

*
Viral Damage
• Some animal viruses enter the host cell and
permanently alter its genetic material resulting in
cancer – 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
*
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

*
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

*
Multiplication of Bacteriophage
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

E. coli
7 Release of
Bacteriophag host
viruses
e

Bacteri Vira
Lysogenic al l
State DNA DN
A 1 Adsorption

Viral DNA 2 Penetration 6 Lysis of weakened


becomes cell
latent as
prophage.
Lytic
Cycl
e

Splice
DNA d
split viral
s genom 3 Duplication of phage 5 Maturatio
e
components; replication n
of
Vira Bacterial
l DNA
virus genetic material
DN molecule
A

Capsid
DN
The lysogenic state in A
bacteria.
The viral DNA molecule is
inserted at
+
specific sites on the bacterial Tail Tail fibers
chromosome. The viral DNA is 4 Assembly Sheath
duplicated along with the regular of
genome and can provide adaptive new virions

genes for the host bacterium.


Bacteriophag
e

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
Comparison of Bacteriophage and Animal Virus
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Hea
d

Bacteria
l
cell wall
Tub
e
Viral nucleic
acid

Cytoplas
m
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

*
© 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
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
• Why is this property of some viruses so important and
what affect does it have on the spread of some diseases?
*
Lytic and Lysogenic Lifecycles
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

E. coli
7 Release of
Bacteriophag host
viruses
e

Bacteri Vira
Lysogenic al l
State DNA DN
A 1 Adsorption

Viral DNA 2 Penetration 6 Lysis of weakened


becomes cell
latent as
prophage.
Lytic
Cycl
e

Splice
DNA d
split viral
s genom 3 Duplication of phage 5 Maturatio
e
components; replication n
of
Vira Bacterial
l DNA
virus genetic material
DN molecule
A

Capsid
DN
The lysogenic state in A
bacteria.
The viral DNA molecule is
inserted at
+
specific sites on the bacterial Tail Tail fibers
chromosome. The viral DNA is 4 Assembly Sheath
duplicated along with the regular of
genome and can provide adaptive new virions

genes for the host bacterium.


Bacteriophag
e

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
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
– Corynebacterium diphtheriae
– Vibrio cholerae
– Clostridium botulinum

*
How do we grow viruses?
Obligate intracellular parasites
– what do they need to grow?

They require appropriate cells to


replicate.
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

*
Methods for Growing Viruses

Inoculation
of amniotic
Inoculatio cavity
n
of embryo Air
sac Inoculation
of
chorioallanto
ic
Amnio membrane
n

Shel Inoculation
l of
Allantoi
yolk sac
c
cavity
Albumi
n *
(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
• Possible connection of viruses to chronic
afflictions of unknown cause
• Viruses are major participants in the earth’s
ecosystem – How if viruses are not “alive” ?

*
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

*
Prions and Other Infectious Particles
Prions - misfolded proteins, contain no nucleic acid
– Extremely resistant to usual sterilization
techniques
– Cause transmissible spongiform
encephalopathies – fatal neurodegenerative
diseases

*
Prions Diseases
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Common in animals:
• Scrapie in sheep
and goats Brain
cell
• Bovine Prion
spongiform fibrils

encephalopathies
(BSE), a.k.a. mad © James King-Holmes/Institute of Animal Health/Photo Researchers, Inc.

cow disease (a
)
• Wasting disease in
elk
• Humans –
Creutzfeldt-Jakob
Syndrome (CJS)
*
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

*
Concept Check:
Exposure to Nucleases that degrade DNA and RNA would
damage all of the following EXCEPT
A. Animal Viruses
B. Bacteriophage
C. Prions
D. Satellite Viruses
E. Viroids
Group Activity

• 1. Viruses are defined as being


“obligate intracellular parasites”. Are
they also pathogens? Why or Why
not?
• 2. Explain what is meant by host range
of viruses? What governs host range?
What is meant by tissue tropism?
• 3. Describe the independent
characteristics of life viruses exhibit *
Just a reminder………. Exam A
Chapters 1, 3, 4 & 6

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