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MM 526-541

Table of Contents



1.    To contrast the mechanisms of viral pathogenicity with those of bacterial pathogenicity.

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)

Discussion of Virus Pathogenicity

Generally, the virulence of pathogenic bacteria is directly related to the ability of the organism to produce one or more toxins. However, the virulence of viruses is not well defined. A number of factors contribute to the virulence (pathogenicity) of a particular strain of virus. Some viruses enter host tissues directly by trauma or insect bite, but most infections start on the mucous membranes of the respiratory and alimentary tracts. To initiate infection, virus particles must first survive on these mucous-covered membranes in the presence of viral and non-viral commensals. Subsequently, to replicate, the virus must enter host cells either in the mucous membrane itself or in tissues farther afield after penetration through the surface membrane. Replication in mucous membrane cells can produce the disease effects directly as in respiratory diseases, but sometimes it provides a staging post for subsequent damaging replication in another site, e.g., polio virus replicates first in the alimentary tract cells and ultimately in anterior horn cells of the spinal cord.

The host anti-viral defense mechanisms include:

A.     Non-specific host defense mechanisms

B.     Specific host defense mechanisms How virulent viruses overcome these non-specific and specific virus inhibitors is unknown. They do bypass these inhibitors and infect the mucosal cells in certain diseases (influenza, common cold). Other viruses pass through the mucosa without establishing infection in the membrane itself, but infect other body tissues.

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

Host Damage

Cell lysis

Assuming that a virus can enter a cell and complete its normal replication cycle, what are some specific temporary or permanent damages incurred by the cell? The most obvious is cell lysis. This may occur due to a physical internal pressure exerted by the multiplying virus. The cell becomes filled with virus and merely bursts. This is common with bacterial viruses, but not with animal viruses. With animal viruses, cell lysis is usually the result of one of four types of allergic reactions:

Production of toxic substances

During the course of virus replication, many viral components as well as by-products of viral replication accumulate in the cell. These are often cytotoxic (e.g., Vaccinia virus in HeLa cells). The molecular mechanism of these toxins is not known in most cases. Only gross morphological defects can be observed generally. Some examples are:

Cell transformation

Certain viruses have the ability to enter a cell and follow one of two alternative courses. They either multiply in a normal manner and are eventually released from the cell, or they may be dormant in the cell and eventually transform the cell into a malignant cell. It is believed that the transformation process involves the integration of viral nucleic acid into the host chromosome. When this happens, the cell achieves certain characteristics of malignant cells.

Suppression of the immune mechanisms

Since many viruses are known to replicate in cells of the lymphoreticular system, it is possible that these viruses can affect the immune system. Viruses or virus-like particles have been found in the thymus, lymph nodes, spleen, bone marrow, stem cells, plasma cells, lymphocytes, macrophages, monocytes, polymorphonuclear leukocytes and Kupffer cells. The nature and extent of the immunologic alteration depends on the organ or cell type infected and the species of virus causing the infection. These effects have been demonstrated in each of the following systems.

1.    Humoral Immunity

2.    Cellular immunity 3.    Reticuloendothelial system and phagocytosis No theories have been proposed to account for the effects of viruses on the RES.

Induction of non-normal host-specified products

Virus-infected cells, at times, will produce compounds coded for by the host DNA, but which are not normally produced by the host. These are often cytotoxic at relatively high concentrations. Other host compounds which are normally found in low concentration may be produced in higher concentration during a virus infection. Again, this high concentration may be cytotoxic. Some virus-induced products release autolytic enzymes from the cells own lysosomes.

Induction of structural alterations in the host cell

Viruses can induce structural alterations in the host cell's cytoplasm and nucleus. These are often of diagnostic importance.

1.    Cytoplasmic changes

2.    Nuclear changes 3.    Membrane changes


1.    Most commonly viral damage to the host cell is manifested as cell lysis mediated by one or more of four types of allergic reactions.

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

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.

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