Pathogenesis of virus 

The term “pathogenesis” covers the factors that contribute to the origins and development of a disease. In the case of viruses, the infection is by a par­enteral or mucosal route. The viruses either replicate at the portal of entry only (local infection) or reach their target organ hematogenously, lympogenously or by neurogenic spread (generalized infection). In both cases, viral replication induces degenerative damage. Its extent is determined by the extent of virus-induced cell destruction and sets the level of disease manifestation. Immunological responses can contribute to elimination of the viruses by destroying the infected cells, but the same response may also exacerbate the course of the disease.

Transmission. Viruses can be transmitted horizontally (within a group of individuals (Table 1) or vertically (from mother to offspring). Vertical infec­tion is either transovHelvetica or by infection of the virus in utero (ascending or diaplacental). Connatal infection is the term used when offspring are born infected.

Portal of entry. The most important portals of entry for viruses are the mucosa of the respiratory and gastrointestinal tracts. Intact epidermis presents a barrier to viruses, which can, however, be overcome through microtraumata (nearly always present) or mechanical inoculation (e.g., bloodsucking arthropods).

Viral dissemination in the organism. There are two forms of infection:

-Local infection. In this form of infection, the viruses spread only from cell to cell. The infection and manifest disease are thus restricted to the tissues in the immediate vicinity of the portal of entry. Example: rhinoviruses that re­produce only in the cells of the upper respiratory tract.

-Generalized infection. In this type, the viruses usually replicate to some extent at the portal of entry and are then disseminated via the lymph ducts or bloodstream and reach their target organ either directly or after infecting a further organ. When the target organ is reached, viral replication and the re­sulting cell destruction become so widespread that clinical symptoms devel­op. Examples of such infection courses are seen with enteroviruses that replicate mainly in the intestinal epithelium, but cause no symptoms there.

Table 1: Horizontal Transmission of Pathogenic Viruses

Clinical symptoms in these infections first arise in the target organs such as the CNS (polioviruses, echoviruses) or musculature (coxsackie viruses).

Another mode of viral dissemination in the macroorganism is neurogenic spread along the nerve tracts, from the portal of entry to the CNS (rabies), or in the opposite direction from the ganglions where the viruses persist in a latent state to the target organ (herpes simplex).

Course of infection. The organ damage caused by viruses is mainly of a de­generative nature. Inflammatory reactions are secondary processes. The se­verity of the clinical symptoms depends primarily on the extent of virus-in­duced (or immunological, see below) cell damage. This means most of the viral progeny are produced prior to the occurrence of clinical symptoms, with consequences for epidemiology and antiviral therapies. It also means that infections can go unnoticed if cell destruction is insignificant or lacking entirely. In such cases, the terms inapparent, silent, or subclinical infection are used, in contrast to apparent viral infections with clinical symp­toms. Virus replication and release do take place in inapparent infections, as opposed to latent infections, in which no viral particles are produced.

Immunological processes can also influence the course of viral infections, whereby the infection can be subdued or healed. On the other hand, the infection may also be exacerbated, either because immune com­plexes are formed with viruses or viral components (nephritis) or because the immune system recognizes and destroys virus-infected cells. This is pos­sible if viral antigens are integrated in the cell membrane and thus expressed on the cell surface. These processes become pathologically significant in cases in which the viruses themselves cause little or no cell destruction.

Virus excretion. Excretion of newly produced viruses depends on the loca­lization of viral replication. For example, viruses that infect the respiratory tract are excreted in expired air (droplet infection). It must be remembered that in generalized infections not only the target organ is involved in excre­tion, but that primary viral replication at the portal of entry also contributes to virus excretion (for example enteroviruses, which replicate primarily in the intestinal wall and are excreted in feces). Once again, since the symptoms of a viral disease result from cell destruction, production, and excretion of new virus progeny precede the onset of illness. As a rule, patients are therefore contagious before they really become ill.

References

Fritz H. Kayser, M.D. Emeritus Professor of Medical Microbiology Institute of Medical Microbiology, University of Zurich, Zurich, SwitzerlandThieme 2005, Stuttgart ! New York.