Lecture 8.

MIC 315

Infectious Diseases and Diagnostic Microbiology

Pathogenic Properties of Viruses
The pathogenic properties of viruses depend on:

q Their gaining access to a host,

q Evading the host’s defenses, and

q Causing damage to or death of the host cell while reproducing themselves.

Viral Mechanisms for evading Host Defenses
q Viruses have a variety of mechanisms that enable them to evade destruction by the host’s immune
response. For example,

ü Viruses can penetrate and grow inside host cells, where components of the immune system
cannot reach them.

ü Viruses gain access to cells because they have attachment sites for receptors on their target cells.
When such an attachment site is brought together with an appropriate receptor, the virus can bind
to and penetrate the cell.

ü Some viruses gain access to host cells because their attachment sites mimic substances useful to
those cells. For example, the attachment sites of rabies virus can mimic the neurotransmitter
acetylcholine. As a result, the virus can enter the host cell along with the neurotransmitter.
q The AIDS virus (HIV) goes further by hiding its attachment sites from the immune response and
by attacking components of the immune system directly.

ü Like most viruses, HIV is cell specific, in this case attacking only particular body cells that have a
surface marker called the CD4 protein.
ü Most of these cells are immune system T cells (T lymphocytes). Binding sites on HIV are
complementary to the CD4 protein.
ü The surface of the virus is folded to form ridges and valleys, and the HIV binding sites are located
on the floors of the valleys.
ü CD4 proteins are long enough and slender enough to reach these binding sites, whereas antibody
molecules made against HIV are too large to make contact with the sites.
ü As a result, it is difficult for these antibodies to destroy HIV.
Cytopathic effects of Viruses
q Infection of a host cell by an animal virus usually kills the host cell.

q Death can be caused by the accumulation of large numbers of multiplying viruses, by the
effects of viral proteins on the permeability of the host cell’s plasma membrane, or by
inhibition of host DNA, RNA, or protein synthesis.

q The visible effects of viral infection are known as cytopathic effects (CPE).

q Those cytopathic effects that result in cell death are called cytocidal effects; those that
result in cell damage but not cell death are called noncytocidal effects.

q CPEs are used to diagnose many viral infections.

q Cytopathic effects vary by virus.

q One difference is the point in the viral infection cycle at which the effects occur.

q Some viral infections result in early changes in the host cell; in other infections, changes
are not seen until a much later stage.
Figure: Some cytopathic effects of viruses:

a) Cytoplasmic inclusion body in brain tissue from a person who died of rabies.

b) Portion of a syncytium (giant cell) formed in a cell infected with measles virus.
The cytoplasmic mass is probably the Golgi complexes of fused cells.
 Example of CPE by Vaccinia virus

NCI-H460 NCI-H460 + Vaccinia virus

A virus can produce one or more of the following cytopathic effects:
1. The macromolecular synthesis within the host cell stops. Some viruses, such as herpes
simplex virus, irreversibly stop mitosis.

2. Host cell lysosomes are made to release their enzymes, resulting in destruction of intracellular
contents and host cell death.

3. Inclusion bodies are found in the cytoplasm or nucleus of some infected cells. These granules
are sometimes viral parts-nucleic acids or proteins in the process of being assembled into
virions. The granules vary in size, shape, and staining properties. They are characterized by their
ability to stain with an acidic stain (acidophilic) or with a basic stain (basophilic). Other
inclusion bodies arise at sites of earlier viral synthesis but do not contain assembled viruses or
their components.
Inclusion bodies are important because they can help identify the causative agent.
ü For example, in most cases, rabies virus produces inclusion bodies (Negri bodies) in the
cytoplasm of nerve cells, and their presence in animal brain tissue has been used as one
diagnostic tool for rabies.
ü Diagnostic inclusion bodies are also associated with measles virus, vaccinia virus, smallpox
virus, herpesvirus, and adenoviruses.

4. At times, several adjacent infected cells fuse to form a very large multinucleate cell called a

syncytium. Such giant cells are produced from infections by viruses that cause measles,
mumps, and the common cold.
5. Some viral infections result in changes in the host cell’s functions with no visible changes in
the infected cells. For example, when measles virus attaches to its receptor called CD46, the
CD46 prompts the cell to reduce production of a cytokine called IL 12, reducing the host’s
ability to fight the infection.

6. Many viral infections induce antigenic changes on the surface of the infected cells. These
antigenic changes elicit a host antibody response against the infected cell, and thus they target the
cell for destruction by the host’s immune system.

7. Some viruses induce chromosomal changes in the host cell. For example, some viral
infections result in chromosomal damage to the host cell, most often chromosomal breakage.
Frequently, oncogenes (cancer-causing genes) may be contributed or activated by a virus.
Figure: Human fibroblast are transformed by Rous sarcoma virus. Normal fibroblasts grow as flat, spread-
out cells.
8. Viruses capable of causing cancer transform host cells. Transformation results in an
abnormal, spindle-shaped cell that does not recognize contact inhibition, meaning cells don’t
stop growing when they come in close contact with other cells. The loss of contact inhibition
results in unregulated cell growth.

9. Some virus-infected host cells produce substances called alpha and beta interferons. Viral
infection induces cells to produce these interferons, but the host cell’s DNA actually codes for
them.
q Alpha and beta interferons protect neighbouring uninfected cells from viral infection in
two ways: (1) they inhibit synthesis of viral proteins and host cell proteins; and (2) they kill
virus-infected host cells by apoptosis (programmed cell death). However, almost all viruses
have mechanisms that evade interferons by partially blocking their synthesis.
Some representative viruses that cause cytopathic effects are presented in the following table.