MM
526-541
2. To develop the concept of the target organ in viral pathogenicity.
3. To stress the role of immune mechanisms in virus-induced cell damage.
4. To define the role of viruses in teratology.
Specific educational objectives (terms and concepts upon which you will be tested)
B. Ability to grow within the cell
C. Ability to combat host defense mechanisms
D.
Ability to produce temporary or permanent damage in the host via:
2. Production of toxic substances
3. Cell transformation
4.
Induction of formation of substances which are not specified by the viral
genome, but are apparently
cellular products normally not produced by the cell.
5. Induction
of structural alterations in the host cell
(b) Cytoplasmic
The host anti-viral defense mechanisms include:
A. Non-specific host defense mechanisms
2.
Cellular factors
2. Activated phagocytes
Although ability to replicate in host tissues is not the only factor in virus virulence, it is essential, and the more rapid the rate of replication, the more likely the success of the virus in producing its disease syndrome. Ability to proliferate in vivo depends on an inherent ability to replicate in the biochemical conditions of the host tissues, coupled with a capacity to resist or not to stimulate host defense mechanisms which would otherwise kill or remove them. The ability of a virus to replicate in a particular cell depends on inherent features of the cell as well as the virus. These features can be involved in one or more stages of replication:
A. Attachment
C. Uncoating
E. Synthesis of precursors of low molecular weight compounds
F. Nucleic acid and protein synthesis
G. Assembly
H. Release
2.
Type II. IgG and/or IgM antibodies are involved in this reaction. The effects
can be of two types:
(b)
A virus component, commonly the capsid protein, is expressed on the surface
of the infected cell.
Antibody and complement bind to this infected cell and cause a lysis of
that cell. This is thought to be
the major mechanism of viral-induced cell lysis.
The III reactions are known as Arthus-type
reactions. The classical
symptoms of this type of
hypersensitivity are edema, polymorphonuclear leukocyte infiltration and
hemorrhage. These are followed
by secondary necrosis which reaches a maximum in 8-24 hours. This type
of hypersensitivity is due to
precipitating antibody only, and requires a large amount of antibody. The
antibody is not fixed to the
tissues. Histamine does not duplicate the reaction and antihistamines do
not suppress the reaction.
4.
Type IV. This type of allergic reaction does NOT involve antibody. Sensitized
T-lymphocytes react directly
with viral antigen, usually that antigen expressed on the surface of an
infected cell, producing
inflammation through the action of lymphokines. This leads to lysis of
the infected cell. This is a delayed-type
hypersensitivity which results in the Zinkernagel-Dougherty phenomenon.
This is probably the second most
common allergic reaction to viruses.
2.
Herpesvirus components produce syncytia
(multi-nucleated protoplasmic mass, seemingly an aggregation
of numerous cells without a regular cell outline).
3. Penton of adenovirus causes host cell rounding and cell detachment from glass.
4.
A double-stranded RNA from enterovirus causes rapid death, without the
production of infectious virus, of
cells susceptible and unsusceptible to enterovirus infection.
5. The fiber antigen of the adenovirus capsid inhibits RNA, DNA and protein synthesis.
6.
Large quantities of some viruses, such as influenza virus and poxviruses,
cause rapid toxic effects in some
animals.
1. Humoral Immunity
(b)
Viruses which do not produce leukemia but infect lymphoid tissue also decrease
the immune response of
the host. Again in animal model systems, the lymphocytic choriomeningitis
virus, the Argentinian
hemorrhagic fever virus and the Aleutian mink disease virus all cause a
lessened antibody (IgM and IgG)
response to a variety of antigens. Depression of the immune response is
greatest in adults, temporary in
neonates and absent in chronic virus infections.
(c)
Both leukemia and lymphoma viruses also decrease the ability of an animal
to undergo anaphylaxis. This is
thought to be due to a reduced synthesis of IgE.
Many
theories have been proposed to explain how viruses depress immune function.
Since these are only theories at the present, only the more common ones
are worth mentioning.
(b) Viruses depress cellular protein (antibody) synthesis.
(c) Viruses destroy antibody-producing cells.
(d) Viruses increase immunoglobulin catabolism.
(b)
Many viruses promote the growth of tumors which would normally be rejected
by the host's cellular immune
mechanisms.
(c)
More relevant to human medicine is the fact that infection with measles
virus, influenza virus, chickenpox
virus, polio virus or rubella virus causes a depression of delayed hypersensitivity
as measured by skin
reaction to tuberculin.
The major theory explaining these phenomena relates the reduced cellular
immunity to a depressed ability
to undergo lymphocyte blast transformation.
(b)
Infection of animals with Venezuelan equine encephalitis virus, Friend
leukemia virus or Moloney leukemia
virus augments clearance of carbon particles.
(c)
Infection of human polymorphonuclear leukocytes with mumps virus, influenza
virus or Coxsackie virus
decreases the ability of these cells to engulf bacteria.
1. Cytoplasmic changes
(b)
Myxoviruses (influenza, fowl, plague) cause cytoplasmic vacuolization,
contraction and degeneration.
"Buds" appear on cell surface.
(c) Myxoviruses (mumps, NDV) cause eosinophilia and Feulgen-negative cytoplasmic inclusions.
(d) Reovirus and measles virus cause eosinophilia.
(e) Poxviruses cause formation of Feulgen-positive cytoplasmic inclusions which contain virions.
(f) Herpesvirus causes vacuolization.
(b) Nuclear inclusion (bodies in the nucleus); e.g., herpesvirus, adenovirus.
(c) Margination and coarsening of chromatin; e.g. herpesvirus, poxvirus.
(d) Polykaryocytosis (many nuclei in the same cytoplasmic field); e.g., herpesvirus and measles virus.
(e) Formation of chromosomal bridges. e.g. herpesvirus and polyoma virus.
(f)
Formation of chromosomal breaks. If both chromatids are broken, the break
is complete. If only one
chromatid is broken, the break is partial. A second important characteristic
that has been used in the
classification of chromosomal breaks is dependent on whether or not healing
or reunion has occurred in the
broken ends. If no reunion has occurred, then there is a gap or a terminal
deletion. If reunion occurs in
other than the original position, then a structural rearrangement is the
result.
(g) Structural rearrangements of chromosome:
(2) Dicentric chromosomes
(3) Interlocking ring chromosomes
(4) Dicentric chromosome resulting from involvement of only one chromatid
(5)
Chromosome arms or branches
(2)
Changes in mitotic mechanism. This is seen in virus-induced persistence
of nucleoli during mitosis.
The end result is a change in chromosome number. Normally, nucleoli disappear
during mitosis and
then reappear at telophase. However, in cells treated with inhibitors of
DNA synthesis or infected with
certain viruses, the nucleolus is visible during mitosis. The importance
of the persistent nucleolus is
that the nucleolus is formed at specific areas of chromosomes, the nucleolus
organizer, and then it
persists, it joins together and two chromatids of these chromosomes and
produces separation
difficulties during anaphase, which may result in nondisjunction.
(3)
Induction of mitotic delay or mitotic inhibition. This is a frequently
observed phenomenon in acute
virus infections of cells in cultures, although it appears to be a non-specific
phenomenon.
2. Type II allergic reactions involving IgG and/or IgM are the major mechanism of viral-induced cell lysis.
3.
Type IV allergic reactions not involving antibody are the second most common
mechanism of viral-induced cell
lysis.
4. A few species of viruses produce viral components which are toxic to the human host cell much like some products of bacteria.
5. Certain species of viruses have the ability to transform a benign cell to a malignant cell via integration of the viral nucleic acid into the human chromosome.
6. Selected species of virus have the ability to alter human immune responses (humoral and cellular) via alteration of immune cell metabolism or immune cell lysis.
7. Some species of viruses "turn on" or activate host cell genes to overproduce the gene product. This product can be cytotoxic in high concentrations.
8. A great number of viral species induce cytoplasmic and/or nuclear changes in their host cells which can be used by the pathologist in diagnosing viral infectious diseases.