Viral pathogenesis

Viral pathogenesis refers to the interaction of the

viral and host factors that leads to disease
production. The virus is said to be pathogenic for
Viral
particular hosts if it can infect and cause sings of
disease in that host. Therefore, the pathogenicity
pathogenesis
is the severity f the disease caused by different
groups of viruses e.g. rabies is ore pathogenic
than measles, hemorrhagic fever virus (HFV) is
more pathogenic than hepatitis B virus (HBV).
More than 300 distinct viruses are known to infect
human and causes as many as 50 syndromes.
Virulence is the severity the disease
caused by different strains of the same virus
group e.g. wild-type and laboratory adapted oral
poliomyelitis virus.
On the other hand, viruses that fail to
produce any symptoms in the host are said to be
inapparent or subclinical, and in fact most viral
infections do not result in the production of
disease.
 Steps in viral pathogenesis
So, the virulence characteristics are those enable the virus to initiate infection, spread in the
body and replicate to large enough number and impair the target organ. These include the
ability of the virus to replicate under certain circumstances, during inflammation, during febrile
.response, in migratory cells and in the presence of natural body inhibitors and interferon
:Steps in viral pathogenesis
.Viral entry to the host and viral pathogenesis .1
.Viral spread and cell tropism .2
Cell injury and clinical illness .3
.Viral shedding .4
:These steps are influenced by many factors which include
Extent to which body tissues and organs are accessible to the virus. The accessibility again.1
:may influenced by
Physical barriers (skin, mucous membranes) .1
.The distance to be traversed in the body .2
.Natural defense mechanisms of the body .3
:Capabilities of the cells to support virus replication and this depend on .2
.a. The presence of specific attachment site (receptors)
.b. Suitable intracellular environment that permits virus replication and release
.c. Effectiveness of host defense
 Steps in viral pathogenesis
.The virulence of the infecting virus .3
To cause disease the infecting virus must be able to overcome the inhibitory effect of
physical barriers, distance, host defense and different cellular susceptibilities to
.infection
:Viral entry (implantation) and primary replication
Viruses may enter the host body by all possible routes(air, food, bite, contaminated
objects, injuries), and all possible site of implantation the body may be used (body
surface, internal sites y mechanical penetration). The implantation is greatest
where the virus in direct contact with living cells (respiratory tract, intestinal tract,
and subcutaneous tissues). The final outcomes of implantation may be influenced
:by
1. Dose infectivity and virulence of the virus.
2. Location of implantation.
Implantation in the fetus (vertical transmission) may occur at a time of:
1. Fertilization via infected germ cells (e.g. HIV)
2. Gestation via the placenta ( e.g. HIV, cytomegalovirus, rubella).
3. At birth (around the delivery- perinatal- e.g. HBV).
 Examples of local viral infections

Site of shedding Target organ Route of spread Site of implantation Virus

RT RT local Respiratory Influenza

tract (RT)
viruses
Parainfluenza
Common cold

AT AT Local Alimentary tract (AT) Rotavirus

Entero viruses

Skin & mucosa Skin & mucosa local Skin & mucosa Human
papilloma
viruses
 Viral pathogenesis
•
3.Viral spread and tissue tropism:
After implantation, viruses are established themselves and start replication at the site of
entry. Spreading from the initially infected cells occur through:
a. Extracellular fluid (most viruses)
b. Intracellular spread: which occur through:
1. Fusion of infected cell with the adjacent non-infected cells.
2. Cytoplasmic bridges between cells.
These types of viral spread provide partial protection to the viruses (e.g. Herpes viruses,
Paramyxo viruses & Pox virus).
Viral spread beyond the adjacent cells occur through:
a. Liquid spaces within the local site e.g. lymphatics
b. Diffusion through surface fluid e.g. mucous layer of respiratory tract.
c. Infected migratory cells(lymphocytes & macrophages).
Establishment of infection at the portal of entry may be followed by:
1 .Localized disease
2. Disseminated disease
3 .Both local and disseminated disease.
 Viral pathogenesis
The localized disease result from continued viral multiplication and localized shedding
(the site of implantation, target organs and site of shedding of the virus are the
same).
In disseminated disease, spread from the portal of entry may occur through 1. Blood
stream: is the most common route of systemic spread of viruses.
Dissemination in nerves- although it is less common, but it is the way of spread in a
number of important viruses (rabies, herpes viruses, and occasionally poliomylitis).

Tissue tropism: (tissue specificity):

The affinity of a virus for a particular tissue. This affinity is determined y:
1. Presence of specific cell receptor & ability of he cell to support virus replication (e.g.
HIV-CD4+ cells, rabies- acetylcholine receptor).
2. Physical barriers & host defense
3. Local temperature, PH, O2 tension.
4. Presence of specific cell trascriptional factors that require enhancer sequence within
the viral genome (e,g, HBV enhancer activity is most active in hepatocytes).
 Viral pathogenesis
4.Cell injury and clinical illness:
The viral replication in the target organ resembles replication at other body sites with
the result of clinical disease. The local recovery mechanisms (local body defense)
which include interferon, local inflammatory reaction & local immunity may
account for the termination of viremia, or may be too late to prevent seeding of
viruses into the target organ & then to the site of shedding. The outcomes of viral
multiplication in the target organ may depend on the balance between the virus
and the host immune response.
a. Sufficient multiplication of the virus in target organ leads to dysfunction
manifested by disease or death e.g. HFVs.
b. Diffusion of toxic products of the viral replication & cell necrosis due to the
release of cytokines & other inflammatory mediators may lead to constitutional
signs e.g. fever, malaise.
Viral antigens may evoked an immune response leading to disease manifestations
e.g.HBV. Impairment of the immune response or immunosuppression caused by
certain viruses may cause secondary opportunistic infections (e.g.influenza, HIV,
measles).
 Incubation period
The time between exposure to virus and onset of disease (i.e. from
the time of implantation through dissemination phase ending
with replication in the target organ causes disease
manifestations).
Factors affecting the incubation period:
1. Site of replication (short incubation period in localized disease &
longer in disseminated disease).
2. Target cell involved & nature of the virus (e.g.Togavirus a rapidly
multiplying virus that injected directly to the bloodstream by
insect bite- the incubation period is extremely short). On the
other hand, longer incubation period in persistent infection (e.g.
Scrapie- Kuru diseases).
3. Late or weak immune response (e.g. as in HIV infection).
 Cellular pathogenesis
The effect of the virus on the cells could be divided into:
1.Direct cell damage
2. Indirect cell damage via immune system
3. Transformation to neoplastic state
4. Steady- state non-cytocidal infection

1. Direct cell damage:

Some highly cytocidal viruses causes early cessation of cellular macromolecular synthesis, leading
rapidly to destruction of the cells. These effects could occur through:
a. Shut down of cellular protein synthesis and eventually cell death, e.g. pox virus, herpes
viruses.
b. Accumulation of viral proteins in the cell during replication may have a toxic effect &
contribute to cell damage e.g. Adeno viruses.
c. Formation of inclusion bodies that distort the cell.
d. Viral activation of cellular lysosomal enzymes resulting in autolysis of the cell.
e. Chromosomal alterations lead to cell damage
f. Almost all viruses cause alterations in the cytoplasmic membrane, that may leads to:
1. Syncytium formation, e.g. Paramyxo, Herpes viruses.
2. Expansion of virus –specific antigens on the surface of infected cells.
Inclusion bodies: These are virus-specific
structures produced during viral Inclusion bodies
multiplication within the cell. They may
become larger than the individual virus. Thy
may be situated in he nucleus e.g. herpes
viruses, or in the cytoplasm e.g. pox virus or
both measles virus. They may be:
1. The site of development of virion (viral
factories).
2. Consist of masses of viral particles during
the replication (e.g. pox, reo virus).
3. Remnant of virus multiplication
(intranuclear inclusion bodies of herpes
viruses).
The presence of inclusion bodies may e of
considerable diagnostic value e.g. Negri body
in rabies.
 Indirect cell damage via the immune response .2
(immunopathology)

The adverse effects of the immune response to viral infection may

be involved in the development of pathological changes &
clinical illness.
1.Cytolytic or cytotoxic reaction mediated by antibodies (Abs) when
combined to viral antigens (Ags) on the surface of infected cells.
Abs can also sensitize cells for destruction by killer cells,
polymorph, or macrophages through a process called antibody
mediated cell cytotoxicity (ADCC).
2. Formation of immune complexes reactions.
3. T cell mediated immune reaction (CMI).
4. Autoimmunity: The virus induce immune response directed not
against viral Ags, but also against normal host components
leading to host tissue damage.
Different viruses utilize different possible site for
shedding, however, the most frequent site are the 4. Shedding of the virus:
RT (influenza, measles, respiratory syncytial virus)
& AT (poliomyelitis virus, hepatitis A virus, rota
virus, hepatitis E virus).
Blood and lymph (e.g. arboviruses, HIV,
HBV,hepatitis C virus). HIV & HBV are also shed in
semen and vaginal secretion. Milk is the site for
shedding of HIV and cytomegalovirus (CMV),
which are also shed from urinary tract, genital
tract & saliva.
* Genital tract is a common site of shedding for
HIV, HBV, herpes simplex virus type-2 (HHV-2). By
infecting the sexual partners or the fetus.
* Saliva is the primary site of shedding for rabies
virus.
* Tumor viruses that integrated into the host cell
DNA can be shed through germ cell (e.g. HIV).
Viral infection of the fetus as a target Congenital
organ may be facilitated by some
variables: viral
1. The immune & interferon systems of infections
the fetus are immature. This immaturity
coupled with the partial placental
barriers to transfer of maternal immunity
& interferon.
2. The rapidly developing fetal organs are
highly vulnerable to distraction.
3. The susceptibility to viral replication
may be modulated by the
undifferentiated fetal cells & by hormonal
changes during pregnancy. The most
common vital infections that induce
congenital abnormalities are CMV &
rubella.
(Dissemination through nerves e.g. Rabies)
(Dissemination through blood stream) HBV