Microbiology- a clinical approach by Anthony
Strelkauskas et al. 2010
Chapter 13: Viral pathogenesis

Because viral infections are so prevalent in
humans, health care professionals must
understand the pathogenic mechanisms used
by these pathogens.
 Viral
infections can be:
◦ Acute (rapid and self limiting)
 Sometimes latent infection can develop
◦ Persistent (long term)
 Chronic
 Latent
 Slow
 Transforming (leading to cancer)

Cancer is essentially associated with mutations
that cause uncontrolled growth.
◦ Normal cell undergo contact inhibition.
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
Some viruses can cause cancer in animals
(transforming viruses) by altering control
mechanisms for cell division and cell death or
inactivating genes responsible for suppressing
tumor formation
Oncogenic viruses
An estimated 20% of human cancers involve
viruses.
◦ HBV, HCV: liver carcinoma
◦ EBV: lymphoma
◦ HPV: cervix carcinoma
Cytopathic viruses produce virions and
kill host cells rapidly (cytopathology).
 Noncytopathic viruses produce virions
but do not cause apparent
cytopathology.
 Some viruses do not produce virions or
cause cytopathology but still cause
infection.


Virus induced
changes of
eukaryotic cell
morphology
◦ Cell rounding
◦ Cell aggregation
◦ Inclusion bodies
 Negri bodies in
rabies
◦ Cell fusion
(syncytium)
Normal
rounding
Cell

Incubation period:

Acute infection:

Decline and convalescence
◦ The virus is replicating.
◦ The host is beginning to respond.
 Characterized by rapid production of virions and action of
host defense
 Depending on virus not every infected person develops
symptoms (positive antibody titers without recollection of
an acute infection)
◦ Elimination of virus infected cells
◦ Development of long lasting immune response


Incubation
periods for
viral diseases
vary for
different
viruses.
Some are as
short as
days:
◦ Influenza
◦ Common cold

Some are as
long as years:
◦ AIDS
Days
Weeks
Months
Years
Long lasting protection
against the same virus
type
(days)
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
There are two forms of antigenic variation
(well described for influenza virus):
Antigenic drift: Involves small changes in virion
structure
◦ Results from point mutations
◦ Minor changes
◦ Cross protective immunity still exists

Antigenic shift: Involves major changes in
virion structure
◦ Is due to the acquisition of new genes
◦ This is through co-infection and gene re-assortment
◦ No pre-existing immunity
http://upload.wikimedia.org/wikipedia/commons/c/ca/Antigenic_drift_vs_shift
.png
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Movie clips\13.01_Antigenic_Drift.mov
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Movie clips\13.02_Antigenic_Shift.mov
a.
b.
c.
d.
e.
non-cytopathic
persistent
cytopathic
latent
permissive
A.
B.
C.
D.
E.
antigenic drift
mutational shift
conformational
mutagenesis
antigenic shift
None of the above.
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
Acute viral infections are severe public health
problems.
They are usually associated with epidemics.
They are more often seen in crowded
environments
◦ Schools, nursing homes, military


Often virus is spread before symptoms arise.
Sometimes virus can disseminate to various
tissues, go into latency and later on re-appear
◦ Example: varicella-zoster (chicken pox).
Chicken pox
Shingles
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

Occur when host defenses are either
modulated or completely bypassed.
Virions are produced for months or even
years.
There are variations of persistent infections:
◦ Chronic infection – the infection is eventually
cleared
◦ Latent infection – the infection lasts for life
◦ Slow infections – these infections are usually
associated with fatal brain infections
◦ Transforming – virus infection triggers cancer
development
HBV – liver cirrhosis
EBV
Burkitt
lymphoma
Measles
encephalitis
HSV – cold sores
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
Adaptive host defense mechanisms against viral
infection include cytotoxic T cells.
CTLs detect specific virus infected cells and instruct
the cell to commit suicide.
Some viruses mutate specific proteins making them
unrecognizable (CTL escape mutants).
Some viruses trigger instead suicide of the CTL.
Other viruses infect in areas that lack local adaptive
defense, e.g. top skin layers, brain.


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Three general characteristics:
◦ No large-scale production of virions
◦ Reduced or absent immune response
◦ Persistence of an intact viral genome so infections can
reoccur
Latent viruses can be reactivated years after entry
into host.
Examples are herpes simplex virus and varizella
zoster virus
◦ Use neurons as vehicles
◦ Remain as extrachromosomal elements in the host nucleus


Viruses can spread easily within the body
Blood
◦ “Hematogenous dissemination” with viremia

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
Lymph
Hidden within mobile immune cells
(lymphocytes, monocytes)
Neural network (axons, dendrites)
◦ Peripheral neurons
◦ Olfactory nerve
◦ Blood
central nervous system
central nervous system
central nervous system
1.
2.
3.
4.
5.
Local replication at portal of entry
Primary viremia
Organ replication
Secondary viremia
Organ replication
Viral rashes are result of spread into skin after
viremia.
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

Viral infections can be acute or persistent.
Persistent infections last longer and can be
chronic, latent, slow, transforming
Cytopathic viruses kill host cells when they
release new virions, whereas non-cytopathic
viruses do not cause cell death even though
they are releasing new virions.
Latent viral infections do not produce large
numbers of virions, but these infections can be
reactivated later and release virions.


Viruses can be disseminated (move to other
parts of the infected host’s body) through the
respiratory, digestive, and urogenital tracts as
well as the nervous system. This is reflected in
the skin rashes associated with many viral
infections.
Some oncogenic viruses have been implicated in
the development of malignancies.
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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