Download PATHOGENIC EFFECTS OF VIRUSES

PATHOGENIC EFFECTS OF
VIRUSES
H.A MWAKYOMA, MD
I: BASIC CHARACTERISTICS OF
A VIRUS.
• Are smallest infectious agents (human
pathogens) known.
• Majority can only be seen by electron
microscopy.
• Few largest ones are just visible by light
microscopy.
• Each true virus contains only a single nucleic
acid as its genome, that is DNA or RNA
contained in a protein shell.
 The type of nucleic acid forms one of the bases
for viral classification.
I: BASIC CHARACTERISTICS OF
A VIRUS
• Viruses are incapable of independent
metabolism or reproduction and thus
• are obligate intracellular parasites, requiring
living cells in which they replicate (They are
incapable of growth and division).
• After invading cells, these microorganisms
divert their biosynthetic and metabolic
capacities to the synthesis of viral encoded
nucleic acids and proteins.
 (They make use of the ribosomes of the host cell
in the course of replication.)
I: BASIC CHARACTERISTICS OF
A VIRUS
• Viral replication is controlled entirely by nucleic
acid.
• Viruses lack the genetic information required to
produce energy generating system.
• They are specific in action, i.e. they always infect
particular organ or organism.
• They are unaffected by antimicrobial antibiotics
• They may undergo mutations
II: GENERAL STRUCTURE OF
AVIRUS.
• The nucleic acid is covered by a protein shell
(coat) known as CAPSID (NUCLEOCAPSID).
• The capsid consists of clusters of
polypeptides which form what is known as
CAPSOMERES.
• Some viruses also posses an outer envelope (a
glycoprotein) derived from host cell.
• The mature infective virus particle is called a
viron.
GENERAL STRUCTURE OF
AVIRUS.
• Most of DNA viruses have NO
ENVELOPE with exception of herpes
viruses.
• Most of RNA viruses are ENVELOPED
with exception of PICORNA viruses and
Reoviruses.
GENERAL STRUCTURE OF
AVIRUS
II: GENERAL STRUCTURE OF
AVIRUS.
DNA VIRUSES:
 Poxviruses
 Herpes viruses:HSV-1&2
Chickenpox
Epstein Barr Virus (EBV)
CMV
DNA VIRUSES:
 Adenoviruses
 Papovaviruses:
Papilloma viruses
Polyoma virus
Vacuolating virus
RNA VIRUSES:
PICORNAviruses
 Enteroviruses:
Polioviruses
Coxsackie virus
ECHO virus (Entero Cytopathic Human
Orphan virus)
 Rhinoviruses
RNA VIRUSES:
ORTHOMYXO viruses – cause influenza.
PARAMYXO viruses
•
•
•
•
Parainfluenza virus – cause sore throat
Measles virus
Mumps virus
LTTI (Lower Respiratory Tract Infection) vius
RNA VIRUSES:
Rhabdoviruses
• Rabies virus, etc
III: VIRUSES AND THE TARGET
CELL: (Pathogenic mechanism).

•
•
•
The functional implications of a viral infection
derive from:
The changes directly produced by the virus in
the host cell.
The host tissue reaction to these changes
The response of the immune system both to
the presence of the virus and to the cellular
changes which it has produced.
III: VIRUSES AND THE TARGET
CELL: (Pathogenic mechanism).
• In order to understand how the above changes
occur, the knowledge on how the virus enter into
a host cell and replicate within it is important.
• Viruses must gain access to the interior of a host
cell because they require many of the cell’s
biosynthetic processes for replication.
• The steps in viral replication are as follows.
The steps in viral replication.

Attachment of the virus to the cell
surface membrane.
– Contact between virus and its target cell
occurs more or less randomly.
– Attachment of the virion to the cell surface
will NOT take place UNLESS the surface
membrane of a cell has a specific viral
receptor site which is complimentary to an
attachment site on the surface of the virus.
Example – poliovirus and influenza virus.
The steps in viral replication.

•
•
•
Viral penetration of the host cell membrane.
Once attachment to the plasma membrane of
the target cell has occurred, the virion
becomes engulfed (Viropexis).
This is a temperature and energy dependent
step.
For enveloped viruses, the envelope fuses with
the plasma membrane of the cell and
nucleocapsid is released directly into the
host cytoplasm
The steps in viral replication.

•
•
•
•
Uncoating of the virus particle.
This is the time when the protein capsid
is removed
The viral nucleic acid is uncoated
The term uncoating means exposure of
the viral nucleic acid
NB: Uncoating may never be completed
in Reoviruses
The steps in viral replication.

•
•
Synthesis of nucleic acid and protein.
In DNA viruses, this is a two stage process.
Synthesis of early proteins (takes place in
nucleus) and synthesis of late proteins
(which takes place in cytoplasm). OR
In RNA viruses, it is a one stage process and
takes place in cytoplasm with exception of
Orthomyxoviruses which replicate in
nucleus.
The steps in viral replication.


Assembly of structurally mature viruses
Release of viruses from the host cell
VIRAL LATENCY:
 Certain viruses, especially Herpes virus
group, can remain dormant within the
host cell for long periods.
 The viruses remain intergrated with the
cell genome until triggered by a variety
of stimuli to undergo a period of
replication.
THE EFFECTS OF VIRAL
REPLICATION:
• The effects of viruses on host cells may
undergo morphological changes.
• Viruses often cause disease by killing the
infected cells (Permissive cells). Many
viruses, however, produce disease
without killing infected cells,(Nonpermissive cells) e.g Rota virus.
THE EFFECTS OF VIRAL
REPLICATION:
• Viruses also produce disease by
promoting the release of chemical
mediators that incite inflammatory or
immunological response e.g symptoms of
common cold are due to release of
bradykinin
THE EFFECTS OF VIRAL REPLICATION:
 The effects of viral replication on host
cell during replication include the
following:
 No change: This occurs in the cell in which the viral
infection is of LATENT variety and show no
structural abnormalities.
 The virus infect and persist in cells without
interfering with normal cellular function, a
process known as latency.
THE EFFECTS OF VIRAL
REPLICATION:
• No change: Viruses that establish latent infection can
emerge to produce disease or transmit
infection long after primary infection
 Opportunistic infections are frequently
caused by viruses that have established
latent infections (CMV, HSV) are among
most frequent opportunistic pathogens,
which emerge in persons with impaired cellmediated immunity.
THE EFFECTS OF VIRAL
REPLICATION:
 Cell death: Cell death is an extremely common
outcome of viral infections and the type
of cell affected may play a dominant role
in determining the clinical pattern of
disease e.g. Poliomyelitis (anterior motor
neuron destruction – motor paralysis)
THE EFFECTS OF VIRAL
REPLICATION:

•
•
Alteration of cell surface membrane:
Some viruses, especially the Paramyxovirus
group cause fusion to take place between
infected and non-infected cells with the
formation of Multinucleated Giant Cells.
This is not uncommon in the tissues of patients
suffering from MEASLES, giant cells being
found chiefly (but not exclusively), in lymphoid
tissues.
MEASLES, giant cells cont-• The giant cells are highly characteristic
mulberry-like giant cells known as
WARTHIN-FINKELDY CELLS and may
be useful in the diagnosis of measles in
tissue sections from patients who may
have died from measles pneumonia.
WARTHIN-FINKELDY GIANT
CELL in a lymphnode
THE EFFECTS OF VIRAL
REPLICATION:

•
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The formation of inclusion bodies:
These bodies are strongly eosinophilic in
tissue sections stained with H&E.
There are 2 types of inclusion bodies;
Types of inclusion bodies;
•
Intracytoplasmic inclusions: - are
found in the cytoplasm in cells infected
by:–
–
–
–
Poxviruses – (Guarnieri body)
Paramyxoviruses
Reoviruses
Rhabdoviruses (Nigri bodies in the brain
and spinal cord) in rabies.
Types of inclusion bodies;
•
Intracytoplasmic inclusions:- are
found in the cytoplasm in cells infected
by;
 Herps viruses
 Adenoviruses
Viral Intranuclear inclusion bodies liver
Viral intranuclear inclusion bodies liver
Viral intranuclear inclusion bodiesliver
Viral intranuclear inclusion bodiesspleen
INTRANUCLEAR INCl u.bladder
Cytoplasmic viral inclusion bodiesHSV2
Cytoplasmic inclusion bodiesrabies (Nigri bodies) in neurons
THE EFFECTS OF VIRAL
REPLICATION:
 Cell proliferation: Independent of any oncogenic effect,
some viral infections can cause cells to
proliferate.
 This is commonly seen in self-limiting
disorders e.g. Infectious Mononucleosis
caused by Herpes virus, the EBV of the
targent cell in the B lymphocytes.
 The B lymphocytes proliferate.
Infectious Mononucleosis
Peripheral blood in infectious mononucleosis
(glandular fever)- atypical lymphocytes
PROTECTIVE RESPONSE OF HOST CELLS AGAINST
VIRAL INFECTIONS (Host Response to viral infection):
•

•

Inflammation:lymphocytes (cellular response)
Antibody production:humoral response (Immunoglobulins,
IgG, IgM, IgA)
• Interferon production: These are glycoproteins
Interferon production:• They are produced by the host cell
especially of the macrophage system in
response to viral infections.
• They are not antibodies
• They are specific of the species in which
they are produced (Species specific BUT
not virus specific)
TYPES OF INTERFERON

•
•
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They are 3 distinct types of interferon
known;
Alpha(ά) interferon:- released chiefly
by leucocytes.
Beta(β) interferon:- released chiefly
from fibroblasts
Gamma(γ) interferon:- released by
activated T lymphocytes.
TYPES OF INTERFERON
• NB: Most important inducers of Alpha and
Beta interferon release are viral infections,
but the production can also be triggered
by:- Rickettsiae, Protozoa, Bacterial
endotoxins.
ACTIONS OF INTERFERON
– interferon act by interfering with viral
synthesis
– the protective effect of interferon is not limited
to a single virus because, unlike antibody, it
does NOT interact directly with the virus
– the interferon secreted by an infected cell
diffuses from that cell and binds to a
membrane receptor on the surface on
neighbouring non-infected cell.
ACTIONS OF INTERFERON cont– There is NO inhibition of viral attachment or
penetration of the cell to which interferon has
bound
– The protective effect is mediated through
blocking the translation of viral mRNA in the
host cell Polyribosomes.
FAILURE OF VIRAL
ELIMINATION:
•

Failure to eliminate the virus from the
host cell may lead to a number of
situations. Such infectios can be;
LATENT:– the virus is not normally detected
– the infection persists in occult, quiescent
from the episode of reactivation in the form
of acute, self-limiting illness.
LATENT:examples
• Examples are;- HSV, Herpes zoster
virus(HZV-which causes Shingles or
herpes zoster), Chicken pox which causes
vericella
FAILURE OF VIRAL
ELIMINATION: cont-
PERSISTENT AND SLOW
INFECTION:• The infection persists and causes a
prolonged disease which is slow to
develop (CARRIERS)
 Examples are:- HBV, HCV, CMV
FAILURE OF VIRAL
ELIMINATION: cont-
•
•
•
•
ONCOGENIC:An infection in which part of the viral genome
is incorporated into the host genome, resulting
in MALIGNANT TRANSFORMATION
(CANCER)
Examples are:DNA viruses:
Papilloma viruses:- squamous cell papilloma,
condyloma accuminatum, Carcinoma of the
cervix (HPV)
ONCOGENIC DNA viruses :Examples
• Herpes viruses:- Burkitt’s lymphoma and
Nasopharyngeal carcinoma (EBV),
• Hepatitis B virus (HBV): – Hepatocellular
carcinoma etc
RNA oncogenic viruses:•
•
Hepatitis C virus (HCV):- Hepatocellular
carcinoma
Human T cell Lymphotropic Virus-1
(HTLV-1):- Adult T cell leukaemia etc