A mouse model for studying poxvirus infection and spread

Many of the models developed for the study of viral pathogenesis involve the use of mice. These animals have an excellent immune system, can be infected with many viruses adapted from human diseases, and are relatively inexpensive to use. Frank Fenner's studies on the pathogenesis of mouse pox carried out in the 1950s provided a classic model for experimental study of viral pathogenesis.

Although smallpox virus is extinct in the wild, the recent realization that smallpox has been extensively studied as a weapon, and fears that it may be in the possession of terrorists, brings these classic studies into sharp focus. Further, other animal poxviruses such as monkey pox can infect humans, and human encroachment of tropical habitats has led to significant occurrence of this disease in tropical Africa. Another poxvirus, myxoma virus, is endemic in rabbit populations in South America, and was used in a temporarily successful attempt to control the ecological threat posed by the high rate of rabbit multiplication in Australia. While touted at the time as an example of successful biological control, numerous complications occurred with its use. Thus, this "experiment" is a valuable example of the benefits and problems involved with biological control.

In Fenner's classic study of mouse pox pathogenesis, virus was introduced by subcutaneous injection of the footpad, and virus yields in various organs, antibody titer, and rash were scored. As noted, the basic experiment thus required only careful dissection of the infected animal, measurement of virus titers, and careful observation. The patterns of virus spread and the occurrence of disease symptoms are illustrated in Fig. 3.4.

Of course, the model is just that; it does not completely describe virus infection in the wild. An example of a significant deviation from one "natural" mode of infection is when poxvirus is transmitted as an aerosol, leading to primary infection in the lungs. This is a difficult infection route to standardize and is only rarely utilized. Also, examining single animals in the laboratory ignores the dynamics of infection and the interactions between virus and the population.

Swelling of foot: Early rash: Severe rash:

primary lesion papules ulceration

Fig. 3.4 The course of experimental poxvirus infection in laboratory mice. Virus is inoculated at day 0 in the footpad of each member of a large group of genetically equivalent mice. Mice are observed daily, and antibody titers in their serum are measured. Selected individuals are then killed, and various organ systems assayed for appearance and presence of virus. Note that symptoms of the disease (rash and swollen foot) only become noticeable after a week.

As a consequence, genetic changes in virus and the host, both of which are the result of the disease progressing in the wild, are ignored.

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