2. Introduction
Pathogenesis: the development of morbid condition or of
disease, more specifically the cellular events and reactions
and other pathologic mechanisms occuring in the
development of disease OR the pathologic, physiologic or
biochemical mechanism resulting in the development of a
disease
The ability of viruses to cause disease can be viewed on two
distinct levels:
The Infected Cell
The changes that occur within individual cell
The Infected Patient
The process that takes place in the infected patient
3. The Infected Cell
There are four main effects of virus infection on the
cell
Death
Fusion of cells to form multinucleated cells
Malignant Transformation
No apparent Morphologic or functional change
4. The Infected Cell
Death- primarily death of the cell is due to inhibition of
macromoleule synthesis and secondary may be by DNA
and RNA synthesis inhibition
Fusion of Virus infected Cells- fusion of infected cells
produce multinucleated giant cells as a result of cell
membrane changes probably caused by viral protein
insertion into the membrane.
Malignant Transformation- The term malignant
transformation refers to changes in the growth properties,
shape, and other features of the tumor cell, the following
changes occur when the cell become malignantly
transformed i-e altered morphology, altered growth
control, altered cellular properties and altered biochemical
properties.
5. The Infected Cell
No apparent Morphologic or functional change-
Infection of the cell accompanied by virus
production can occur without morphologic or
gross functional changes, this observation
highlights the wide variations ranging from rapid
destruction of the cell to a symbiotic relatioship
6. The Infected Patient
Viral infection in the person typically has four stages:
1. Incubation period- during which the patient is
asymptomatic
2. Prodromal period- during which non-specific
symptoms occurs
3. Specific-illness period- during which the characteristic
sign and symptoms occur
4. Recovery period- during which the illness wanes and
the patient regains good health
7. Transmission
The main portals of entry are the respiratory,
gastrointestinal, and genital tracts, but through the skin,
across the placenta, and via blood are important as well.
Transmission from mother to offspring (in utero, at the
time of delivery or breast feeding) is called vertical
transmission; all other modes of transmission (e.g., fecal–
oral, respiratory aerosol, insect bite) are horizontal
transmission.
Transmission can be from human to human or from animal
to human.
8.
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10.
11. Localized and Disseminated Infetion
Most viral infections are either localized to the portal
of entry or spread systemically through the body.
The best example of the localized infection is the
common cold caused by rhinoviruses, which involves
only the upper respiratory tract
Most serious viral infection are systemic i.e., the virus
travels from the portal of entry via the blood to various
organs e.g. poliomyelitis and measles
Some viral infections spread systemically, not via the
bloodstream, but rather by retrograde axonal flow
within neurons e.g. Rabies and herpes simplex Virus
12. Pathogenesis
The sign and symptoms of most viral diseases are the
result of cell death by virus e.g. Motor neuron killing
by polio virus or damage to the vascular endothelial
cells by Ebola Virus
there are some diseases that are not caused by the
virus damaging or killing the infected cell e.g.
Rotavirus induced diarrhea caused by enteric nervous
system stimulation
There are other diseases in which cell killing by
immunologic attack plays an important role in
pathogenesis
13. Immunopathogenesis
Immunopathogenesis is the process by which the
symptoms of viral diseases are caused by the immune
system rather than by the killing of cells directly by the
virus.
One type of immunopathogenesis is the killing of virus-
infected cell by the attack of cytotoxic T cells that recognize
viral antigens on the cell surface. Damage to the liver
caused by hepatitis viruses occurs by this mechanism.
Another is the formation of virus– antibody complexes that
are deposited in tissues. Arthritis associated with
parvovirus B19 or rubella virus infection occurs by this
mechanism.
14. Immune Evasion
Viruses have several ways by which they evade our host
defenses
Some viruses encode the receptors for various mediators of
immunity such as interleukin-1 (IL-1) and tumor necrosis
factor (TNF), these virus-encoded proteins that block host
immune mediators are often called cytokine decoys.
Some viruses can reduce the expression of class I MHC
proteins thereby reducing the ability of cytotoxic T cells to
kill the virus-infected cells and other inhibit complements
and some viruses synthesize the RNAs which reduce the
ability of interferon to block viral replication, collectively
these viral virulence factors are called virokines
15. Immune Evasion
A third important way by which viruses evade our host
defenses is by having multiple antigenic types
The classic example of a virus with multiple serotypes
is rhinovirus, which has more than 100 serotypes
17. Persistant Viral Infection
In most viral infections, the virus does not remain in the
body for a significant period after clinical recovery, but in
certain instances, the virus persists for long periods either
intact or in the form of a subviral component (e.g., the
genome), the mechanisms involve are:
Integration of a DNA provirus into host cell DNA
Immune tolerance, because neutralizing antibodies are not
formed
formation of virus–antibody complexes, which remain
infectious
location within an immunologically sheltered “sanctuary”
(e.g., the brain)
rapid antigenic variation
spread from cell to cell without an extracellular phase
immunosuppression
18. Persistant Viral Infection
Carrier state refers to people who produce virus for long
periods of time and can serve as a source of infection for
others. The carrier state that is frequently associated with
hepatitis C virus infection is a medically important
example.
Latent infections are those infections that are not
producing virus at the present time but can be reactivated
at a subsequent time. The latent infections that are
frequently associated with herpes simplex virus infection
are a medically importan example.
Slow virus infections refer to those diseases with a long
incubation period, often measured in years. Some, such as
progressive multifocal leukoencephalopathy, are caused by
viruses, whereas others, such as Creutzfeldt-Jakob disease,
are caused by prions. The brain is often the main site of
these diseases.
Editor's Notes
virulence is the capacity of any infective organism to cause disease and to injure or kill a susceptible host. Strains of viruses differ greatly in their ability to cause disease
