Microbiology- a clinical approach by Anthony Strelkauskas et
al. 2010
Chapter 12: The structure and infection cycle of viruses
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More than 80% of infectious diseases are
caused by viruses.
As a health professional, most infectious
disease that you see will be caused by viruses.
It is important that you have an understanding
of viral structure and the infection cycle cause
by viruses.
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Emerging infectious diseases
◦ Infectious diseases whose incidences have increased
over the past 30 years or threaten to increase
◦ Includes new pathogens not observed before
 Mutated viruses
◦ Includes diseases whose etiology was not established
before
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Re-emerging infectious diseases
◦ Infectious diseases we once thought to have
overcome bounce back
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Viruses are acellular.
They are obligate intracellular parasites.
Viral genome subverts host cell’s machinery to
reproduce.
Viruses depend on host metabolism.
◦ Energy, materials, enzymes
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Viruses infect living cells.
◦ Bacteria (called bacteriophages) and archaea
◦ Plant cells
◦ Animal cells (human cells included in this group).
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They are specific for a certain cell type.
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They are composed of nucleic acids and proteins.
◦ Their genome is either RNA or DNA
◦ Their genome can be single stranded (ss) or double stranded (ds)
Viral nucleic acid is surrounded by a protein coat called a
capsid.
◦ Each capsid is made up of capsomeres.
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Based on the shape of the capsid viruses are classified as
Icosahedral (spherical)
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Helical (Filamentous)
Some viruses are enclosed by a membrane donated from
the host
◦ Enveloped viruses
◦ Naked viruses do not have an envelope.
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Complex
An intact, complete viral particle is called a virion.
donated from host
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Their shape is derived from 20 triangular faces
that make up the symmetric capsid.
Capsid contains spikes, glycoproteins used to
attach to the host cell.
naked virus, no envelope
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Contains 8 segments of
RNA enclosed in
nucleoprotein
Has an additional layer of
protein = matrix protein
Has an envelope with
hemagglutinin (for
binding to host cell in
initial infection) and
neuraminidase (for
release of newly made
virions) embedded
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Mixture of icosahedral
and helical shapes
◦ Many bacteriophages
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Asymmetrical
(irregular) shapes
◦ Tend to be larger
viruses
 Poxviruses
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Many viruses that infect humans and other
animals are enveloped.
Envelopes originate from the host plasma
membrane or membranes of host organelles
into which viral proteins/glycoproteins have
been embedded.
◦ All envelopes have a phospholipid bilayer.
◦ Viral proteins/glycoproteins often serve attachment
to new host cells and are involved in the infection
cycle.
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Genome packaging has an
important role in the
infection.
Viral genomes are
packaged in various ways
including:
◦ Directly in the capsid
◦ Associated with special
nucleic acid binding
proteins (often
accompanied by additional
proteins that connect the
nucleocapsid to the plasma
membrane if enveloped)
Other classification schemes:
•By host cell
•By the way how the virus genome is replicated (Baltimore classification)
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The infection cycle was first worked out in
bacteriophages (bacterial viruses).
◦ Lytic : leading to bacterial cell death
◦ Lysogenic : virus genome is inserted into bacterial
genome; can be reactivated and funneled into the lytic
cycle
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Animal virus infections can be also either lytic
leading to host cell death or become latent by
incorporation into the host genome.
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In a lytic infection, the host cells fills with virions
and bursts.
◦ The result is cell death.
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Lysogenic infections are also known as latent
infections.
◦ The viral genome (in DNA) becomes incorporated into the
host cell’s DNA (provirus).
 It can remain this way for an extended period.
 The host cell lives.
 Upon cell division the viral genome is also duplicated.
◦ Reactivation and active virion production is possible
depending on external stimuli.
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Movie clips\12.01_Lytic_Lysogenic_Cycles.mov
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For animal viruses, there are six steps in lytic
infection:
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Attachment
Penetration/uptake
Uncoating
Biosynthesis
Maturation
Release → Specific for animal virus, absent in bacteriophages
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Attachment occurs when a virion binds
to specific receptors on a host cell.
Some viruses require a co-receptor
Without the co-receptor, there is no
infection.
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Many different host cell
molecules can be used as viral
receptors.
◦ Some viruses use more than one
type.
◦ Some receptors are shared by
many viruses.
◦ Receptors can determine host
range of virus.
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Virus-receptor binding is high
affinity.
◦ There are conformational
interactions.
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Non-enveloped viruses
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Enveloped viruses
◦ Binding takes place between viral
capsid (spikes!) and receptor.
◦ Binding takes place between viral
envelope proteins and receptor.
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Once attached,
the virus must
gain entry to the
host cell.
It must also
uncoat or remove
the capsid.
Uncoating can
occur in three
places:
◦ At the plasma
membrane
◦ In the cytoplasm
◦ At the nuclear
membrane
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Use receptor mediated
endocytosis to gain
entry into the host cell
◦ Virus is enclosed in a
vesicle – the endosome
◦ Endosomes fuse with the
lysosome where uncoating
begins.
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Some viruses form a
pore in the host
membrane.
Non-enveloped viruses
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Envelope fuses with the
host cell membrane
◦ Fusion is mediated by
specialized fusion proteins.
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For some viruses, fusion
requires the presence
of co-receptor
molecules.
Enveloped viruses
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Viral infection requires compartmentalization.
◦ Viral genomes, capsids, and other viral proteins are
synthesized in specific locations in the host cell.
◦ Newly synthesized viral components are moved to other
locations for assembly of viral particles.
Viral components are moved in vesicles, using host
cell microtubules.
DNA viruses or retroviruses transport their
genome into the nucleus.
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Biosynthesis of new viral components can be
complex.
◦ Viral genomes are either DNA or RNA.
◦ Both can be single or double-stranded.
◦ Single stranded RNA viruses can be of (+) or (-)
RNA
◦ Retroviruses have an RNA genome which is
converted into DNA during the replication
process.
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If possible the host cell machinery is used.
Host DNA synthesis is inhibited by the virus.
◦ All polymerases and proteins concentrate on
viral DNA synthesis.
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DNA viruses must go to cell nucleus to use
host polymerase
◦ Or replicate in cytoplasm with viral polymerase
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RNA viruses must encode a viral polymerase
◦ Mostly packaged in the virion
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dsRNA and (+)ssRNA genome can be directly
translated
(-)ssRNA and retrovirus genomes must be
replicated to be able to be translated
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Double-stranded DNA viruses use the same
mechanisms as the host cell for biosynthesis.
◦ One strand of viral DNA is transcribed into mRNA.
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Viral strand is used as a template to make a
complementary copy of DNA.
◦ This uses the host cell’s DNA polymerase.
◦ The complementary copy is transcribed into mRNA.
◦ It is also used to make new copies of the viral
genome.
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Latent viruses do not kill host cells.
The viral genome is inserted into a host
chromosome.
Maximum replication is not required.
◦ A small number of viral genes are expressed.
◦ A limited number of viral genomes are replicated.
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Mechanisms of biosynthesis are more
complicated than in DNA viruses.
Host cells do not possess RNA-dependent
polymerases.
◦ They are required to make viral mRNA and replicate
genomes.
◦ Viruses must carry one.
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Genomes contain one (+) strand and one (–) strand.
During infection, the (–) strand is copied into
messenger RNA.
◦ This is done by a viral RNA polymerase.
◦ The mRNA is used to produce viral proteins.
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Each of the strands is used as a template to make a
new double-stranded genome.
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The (+) strand is already mRNA.
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Genome replication has 2 steps:
◦ It can be directly translated into viral proteins.
◦ The (+) strand is copied into (–) template
◦ The template is used to make more (+) strands.
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The (–) strand cannot be used as mRNA
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The new template strand is mRNA:
◦ It must first be copied into a (+) template strand.
◦ This is done using a viral RNA polymerase packaged
with the virus.
◦ It is used to synthesis viral proteins.
◦ It is also used to make new viral genomes
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Retroviruses are RNA
viruses that contain the
enzyme reverse
transcriptase.
◦ Reverse transcriptase
converts RNA into DNA.
◦ Converted viral DNA can be
inserted into the host cell
chromosome.
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Retroviruses cause
latent infections.
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Movie
Movie
Movie
Movie
Movie
clips\12.02_Biosynthesis1_dsDNA.mov
clips\12.03_Biosynthesis2_ssDNA.mov
clips\12.04_Biosynthesis3_dsRNA.mov
clips\12.05_Biosynthesis4_+ssRNA.mov
clips\12.05_Biosynthesis4_-ssRNA.mov
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Intracellular
trafficking
◦ Involves the
movement of newly
made viral
components to
specific sites in the
host cell.
◦ Transported through
the cell by host cell
microtubules
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Assembly
◦ Site depends on
 The type of genome
(DNA or RNA)
 The mechanism of
genome replication
 The presence or
absence of an
envelope.
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All virions must complete a common set of
assembly reactions.
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Formation of structural subunits for the capsid
Assembly of the capsid
Association of viral genome within the capsid
Enveloped viruses: assembly of viral envelope
glycoproteins.
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New virions can be released from the host cell
in two ways:
◦ Lysis (non-enveloped viruses)
◦ Budding (enveloped viruses)
Budding of influenza virus
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Viruses can spread from cell to cell.
◦ They can use tight junctions between cells (b, c).
apical
basolateral
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Viruses can
spread from
cell to cell.
◦ They can also
spread
through the
formation of
syncytia.
◦ Syncytia are
fused giant
cells filled
with virus.
87 h pi
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Some viruses produce decoy virions.
◦ These are empty capsids or non-infectious virions
◦ They confuse and distract the host defenses.
Some viruses incorporate host proteins as a
type of camouflage.
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Viruses must be cultured within a host cell
◦ Bacteria in culture
◦ Animal cells in tissue culture or eggs
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Host cells form confluent lawn
◦ Viruses form plaques where host cells were lyzed
 Plaque is a colony of viruses
Bacterial
lawn
Confluent
animal
cells
Microbiology: An Evolving Science
© 2009 W. W. Norton & Company,
Inc.
40
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Eclipse: not a single intact virion
present
Latent period: No extracellular
virions detectable
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Rise period: Release of virus
progeny
Burst size: total number of
progeny released per infected
cell.
Microbiology: An Evolving Science
© 2009 W. W. Norton & Company,
Inc.
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Viral structures include nucleic acids (either
DNA or RNA), and a capsid protein coat made
of capsomere subunits.
Some viruses are surrounded by envelopes
composed of viral glycoproteins,
oligosaccharides, and host cell membrane lipids.
Viruses may lyse the host cells by using a lytic
infection cycle or they may employ a lysogenic
infection cycle in which the viral genome is
incorporated into the host cell’s DNA, resulting
in a latent infection.
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A lytic infection cycle involves the steps of
attachment, penetration, uncoating,
biosynthesis, maturation, and release.
Host cell receptors are used to facilitate virus
attachment and entry into host cells.
Synthesis of new viral components involves
complex replication mechanisms of the viral
DNA or RNA.
Intracellular trafficking and assembly of viral
components in the host cell occur during the
maturation stage of the viral infection cycle.
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Newly assembled viruses may be released
through lysis of the host cell or by budding
from the surface of the host cell.
In a one step virus growth curve for a
bacteriophage the eclipse (not a single intact
virion present), latent period (only intracellular
virions) and rise period (virions appear
extracellularly) are key phases.
The burst size is the total number of virions
produced per infected cell.
A.
B.
C.
D.
E.
Reverse
transcriptase
Integrase
Polymerase
A only
A and B
A.
B.
C.
D.
E.
Kills its host
immediately
Forms plasmids in the
host
Releases massive
numbers or virus all at
once
Incorporates its
nucleic acid with that
of the host
chromosome
Causes host cell to
become lytic.
A.
B.
C.
D.
E.
Not a single intact
virion is present.
No extracellular
virions are
detectable.
Release of virus
progeny occurs.
The virus adjusts to
the new surronding.
None of the above.
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11:40am – 1:20pm
Chapters 1 thru 13: Lecture, Reading, Chapter
End Self Study Questions
Fifty Multiple Choice Questions = 100 points
Please bring:
◦ Scantron (form No. 882-E for the Quiz – available at
no cost at the Student Bookstore)
◦ No. 2 pencil only