In laboratory mice, ectromelia virus is infectious by all routes of inoculation; it always produces a generalized infection but there are local lesions in the lungs after intranasal inoculation and in the peritoneal cavity after intraperitoneal injection. The response of mice is strongly conditioned by mouse genotype (see below).

The usual source of natural infection is via minor abrasions of the skin, which may occur from contaminated bedding or during manipulations by animal handlers. Infection may also occur by the respiratory route, but probably only between mice in close proximity to each other. A primary lesion usually develops at the site of infection. Since mice are readily infected by inoculation, virus-contaminated mouse serum, ascites fluid or mouse cells, tumors or tissues constitute a risk to laboratory colonies previously free of infection.

Enzootic mousepox

Mousepox was enzootic in many mouse breeding establishments in Europe and Japan until the 1960s. A variety of mechanisms probably operated to maintain the virus, without so disrupting the mouse breeding program as to make control mandatory. One important factor was probably the high level of genetic resistance and trivial symptomatology exhibited by many mouse genotypes. Another may have been maternal antibody. Another possible mechanism for maintaining enzootic infection is chronic, clinically inapparent infection, which sometimes occurs after oral administration, when some mice show infection of Peyer's patches, excretion of virus in the feces and lesions in tail skin.

Susceptibility of different strains of mice

Analysis of spontaneous epizootics and deliberate experiments in the 1980s showed that C56BL/6 and AKR mice were highly resistant to mousepox and BALB/c, DBA and CH3 mice were highly susceptible. Although there was no clinical evidence of infection in C57BL/6 mice except for the swelling of the inoculated foot, serial transmission between such mice was observed for at least six generations. Strain differences are best demonstrated after footpad inoculation or in natural epizootics, as C57BL mice are relatively susceptible by intranasal, intracerebral or intraperitoneal infection.

Experimental epidemiology

In the early 1920s the British bacteriologist, Topley, embarked upon a long-term study of experimental epizootics in mice housed in specially designed cages. Studies of long-continued epizootics of ectromelia (1.75 and 3.25 years) in herds of mice maintained by the regular addition of normal mice suffered from the fact that the only indication of infection was death. In similar experiments carried out after the demonstration of the nature of the virus and the pathogenesis of the disease, Fenner, working at the Hall Institute in Melbourne, constructed life tables for mice exposed to a virulent and an attenuated strain of virus. In addition, closed epizootics were used to study several parameters of naturally spreading orthopoxvirus infection, such as immunization with vaccinia virus and the effects of old age. More recently, Anderson and May have used the results of the long-term experiments by Greenwood and Fenner in an analysis of the population biology of infectious diseases.

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