Experimental infection of an African dormouse (Graphiurus kelleni) with monkeypox virus.

Suitable animal models are needed to study monkeypox virus (MPXV) as human monkeypox clinically resembles smallpox and MPXV is a zoonotic and potential bioterroristic agent. We have demonstrated that a species of African dormice, Graphiurus kelleni, is susceptible to a lethal infection of MPXV and that MPXV replicated in multiple organs of this species. Following intranasal administration, MPXV replicated locally in the nasal mucosa causing necrosis and hemorrhage with subsequent systemic spread to lymph nodes, spleen, liver, and other tissues where it caused severe necrosis and/or hemorrhage leading to death. The dormouse model was validated for testing prophylactic (Dryvax vaccine) and therapeutic (cidofovir) test articles against intranasal challenges with MPXV.

Human monkeypox: an emerging zoonotic disease.

Zoonotic monkeypox virus is maintained in a large number of rodent and, to a lesser extent, nonhuman primate species in West and central Africa. Although monkeypox virus was discovered in 1958, the prototypic human cases were not witnessed until the early 1970s. Before this time, it is assumed that infections were masked by smallpox, which was then widely endemic. Nevertheless, since the 1970s, reported monkeypox virus infections of humans have escalated, as have outbreaks with reported human-to-human transmission. This increase is likely due to numerous factors, such as enhanced surveillance efforts, environmental degradation and human urbanization of areas where monkeypox virus is maintained in its animal reservoir(s) and, consequently, serve as a nidus for human infection. Furthermore, viral genetic predispositions enable monkeypox virus to infect many animal species, represented in expansive geographic ranges. Monkeypox virus was once restricted to specific regions of Africa, but its environ has expanded, in one case intercontinentally--suggesting that human monkeypox infections could continue to intensify. As a zoonotic agent, monkeypox virus is far less sensitive to typical eradication measures since it is maintained in wild-animal populations. Moreover, human vaccination is becoming a less viable option to control poxvirus infections in today's increasingly immunocompromised population, particularly with the emergence of HIV in Sub-Saharan Africa. An increased frequency of human monkeypox virus infections, especially in immunocompromised individuals, may permit monkeypox virus to evolve and maintain itself independently in human populations.