The absence of herd immunity to orthopoxviruses and the concern that
variola or monkeypox viruses could be used for bioterroristic activities has stimulated the development of
therapeutics and safer prophylactics. One major limitation in this process is the lack of accessible human
orthopoxvirus infections for clinical efficacy trials; however,
drug licensure can be based on orthopoxvirus animal challenge models as described in the "Animal Efficacy Rule". One such challenge model uses ectromelia virus, an orthopoxvirus, whose natural host is the mouse and is the etiological agent of
mousepox. The genetic similarity of ectromelia virus to
variola and monkeypox viruses, the common features of the resulting disease, and the convenience of the mouse as a laboratory animal underscores its utility in the study of orthopoxvirus pathogenesis and in the development of
therapeutics and prophylactics. In this review we outline how
mousepox has been used as a model for
smallpox. We also discuss
mousepox in the context of mouse strain, route of
infection, infectious dose,
disease progression, and recovery from
infection.