VIRUSE AS THE CAUSE OF

DISEASE
Viruses are biological entities that can only thrive and multiply in a host, which is a
living organism such as a human, an animal, or a plant. Some viruses cause disease.
For example, severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2,
causes the disease COVID-19.

A virus may also affect one organism in one way but a different one in another. This
explains why a virus that causes illness in a cat may not affect a human.
Viruses vary in form and complexity. They consist of genetic material, DNA or
RNA, with a coat of protein around it. Some have an additional coat called the
envelope. This may be spiky and helps them latch onto and enter host cells. They can
only replicate in a host.
VIRAL INFECTIONS
Virus infection of higher organisms is the cumulative result of all the processes

of replication and gene expression. Together, these determine the overall course (or
natural history) of each infection.

Infections range in complexity and duration from a very brief, superficial

interaction between the virus and its host to infections that may span the entire life
of the host organism, from before birth to its eventual death.
A very common misconception is that virus infection results in disease. In reality, the
reverse is true only a small minority of virus infections give rise to any disease
symptoms.
TYPES OF INFECTIONS
1. Abortive infection
2. Acute infection
3. Chronic infection
4. Persistent infection
5. Latent infection
PERSISTENT INFECTION

These infections result from a delicate balance between the virus and the host

organism, in which ongoing virus replication occurs but the virus adjusts its

replication and pathogenicity to avoid killing the host.

In chronic infections, the virus is usually eventually cleared by the host (unless the
infection proves fatal), but in persistent infections the virus may continue to be
present and to replicate in the host for its entire lifetime.
The best studied example of such a system is lymphocytic choriomeningitis

virus (LCMV; an arenavirus) infection in mice.

Mice can be experimentally infected with this virus either at a peripheral site (e.g., a
footpad or the tail) or by direct inoculation into the brain.

Adult mice infected in the latter way are killed by the virus, but among those infected by
a peripheral route there are two possible outcomes to the infection:

Some mice die but others survive, having cleared the virus from the body completely.
Outcome is related to the immune response to the virus. In immunosuppressed adult mice
infected via the central nervous system (CNS) route, a persistent infection is established
in which the virus is not cleared (due to the nonfunctional immune system), but
remarkably, these mice are not killed by the virus.

persistent infections may result from the production of defective-interfering (D.I.) particles
(see Chapter 3). Such particles contain a partial deletion of the virus genome and are
replication defective, but they are maintained and may even tend to accumulate during
infections because they can replicate in the presence of replication-competent helper virus.
The production of D.I. particles is a common consequence of virus infection of
animals, particularly by RNA viruses, but also occurs with DNA viruses and
plant viruses.

The presence of D.I. particles can profoundly influence the course and the
outcome of a virus infection. In some cases, they appear to moderate
pathogenesis, whereas in others they potentiate it, making the symptoms of the
disease much more severe.
LATENT INFECTION
This is the ultimate infection! In latency, the virus is able to down regulate its gene
expression and enter an inactive state with strictly limited gene expression and without
ongoing virus replication.

Latent virus infections typically persist for the entire life of the host. An example of such an
infection in humans is herpes simplex virus (HSV).

In nervous system. There, it hides in dorsal root ganglia. Establishing a truly latent infection.

The nervous system is an immunologically privileged site.

But the major factor in latency is the ability of the virus to restrict its gene
expression.

Restricted gene expression is achieved by tight regulation of a-gene expression,

which is an essential control point in herpesvirus replication.

When reactivated by some provocative stimulus, HSV travels down the sensory
nerves to cause peripheral manifestations such as cold sores or genital ulcers. It is
not altogether clear what constitutes a provocative stimulus, but there are many
possible alternatives, including psychological and physical factors.
Sometimes very painful reappearance of disease symptoms for the rest of the

host’s life. Even worse than this, immunosuppression later in life can cause the

latent infection to flare up.

NEOPLASM
Abnormal growth of tissue in a part of the body, especially as a characteristic of
cancer.

Tumor Viruses

Members of six distinct families of animal viruses, called tumor viruses, are capable
of directly causing cancer in either experimental animals or humans.
1. Hepatitis B Viruses

2. SV40 and Polyomavirus

3. Papillomaviruses

4. Adenoviruses

5. Herpesviruses

6. Retroviruses
HEPATITIS B VIRUSES
The hepatitis B viruses, which have the smallest genomes of all animal DNA viruses, specifically
infect liver cells of several species, including ducks, woodchucks, squirrels, and humans. Infection
with hepatitis B virus usually results in acute liver damage. In 5 to 10% of cases, however, the
acute infection is not resolved and a chronic infection of the liver develops. Such chronic
infection is associated with more than a hundredfold increased risk of liver cancer.

Cell transformation by hepatitis B virus is mediated by a viral gene (called the X gene) that affects
expression of a variety of cellular genes that drive abnormal cell proliferation and survival. In
addition, the development of cancers induced by hepatitis B virus is driven by the continual
proliferation of liver cells that results from chronic tissue damage.
SV40 AND POLYOMAVIRUS
Both SV40 and polyomavirus early-region proteins induce transformation by
interacting with host proteins that regulate cell proliferation. For example, SV40 T
antigen binds to and inactivates the host cell tumor suppressor proteins Rb and p53,
which are key regulators of cell proliferation and cell cycle progression.
PAPILLOMAVIRUSES
The papillomaviruses are small DNA viruses that induce both benign and malignant
tumors in humans and a variety of other animal species.

Cell transformation by human papillomaviruses results from expression of two early-

region genes, E6 and E7. The E6 and E7 proteins analogously to SV40 T antigen by
interfering with the function of the cellular Rb and p53 proteins. In particular, E7
binds to Rb, and E6 stimulates the degradation of p53 by ubiquitin-mediated
proteolysis.
ADENOVIRUSES
The adenoviruses are a large family of DNA viruses.

Transformation by the adenoviruses results from expression of two early genes, E1A
and E1B, which are required for virus replication in permissive cells (Figure 15.16).
These transforming proteins inactivate the Rb and p53 tumor suppressor proteins, with
E1A binding to Rb and E1B binding to p53. It thus appears that SV40,
papillomaviruses, and adenoviruses all induce transformation by a common pathway, in
which altering regulation of the cell cycle by interfering with the activities of Rb and
p53 plays a central role.
HERPESVIRUSES
Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus, are associated with
human cancers. Kaposi's sarcoma-associated herpesvirus plays a critical role in the
development of Kaposi's sarcomas, and Epstein-Barr virus has been implicated in
several human malignancies, including Burkitt's lymphoma in some regions of
Africa, B-cell lymphomas in AIDS patients and other immunosuppressed
individuals.
RETROVIRUSES
Members of one family of RNA viruses, the retroviruses, cause cancer in a variety of
animal species, including humans. One human retrovirus, human T-cell
lymphotropic virus type I (HTLV-I), is the causative agent of adult T-cell leukemia.
Transformation of T lymphocytes by HTLV-I results from expression of the viral
gene tax, which encodes a regulatory protein affecting expression of several cellular
growth control genes.

HIV also induce malignancies in immunosuppressed individuals.