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.

Monkeypox virus (MPXV) was discovered in 1958 during an outbreak in an animal facility in Copenhagen, Denmark. Since its discovery, MPXV has revealed a propensity to infect and induce disease in a large number of animals within the mammalia class from pan-geographical locations. This finding has impeded the elucidation of the natural host, although the strongest candidates are African squirrels and/or other rodents. Experimentally, MPXV can infect animals via a variety of multiple different inoculation routes; however, the natural route of transmission is unknown and is likely to be somewhat species specific. In this review we have attempted to compile and discuss all published articles that describe experimental or natural infections with MPXV, dating from the initial discovery of the virus through to the year 2012. We further discuss the comparative disease courses and pathologies of the host species.

Use of electroporation after PV administration provided superior immunogenicity than delivery without electroporation. This study illustrates the power of combined DNA approaches to generate impressive immune responses in humans.

ST-246 was evaluated for activity against cowpox virus (CV), vaccinia virus (VV), and ectromelia virus (ECTV) and had an in vitro 50% effective concentration (EC 50 ) of 0.48 M against CV, 0.05 M against VV, and 0.07 M against ECTV. The selectivity indices were >208 and >2,000 for CV and VV, respectively. The in vitro antiviral activity of ST-246 was significantly greater than that of cidofovir, which had an EC 50 of 41.1 M against CV and 29.2 M against VV, with selectivity indices of >7 and >10, respectively. ST-246 administered once daily by oral gavage to mice infected intranasally with CV beginning 4 h or delayed until 72 h postinoculation was highly effective when given for a 14-day duration using 100, 30, or 10 mg/kg of body weight. When 100 mg/kg of ST-246 was administered to VV-infected mice, a duration of 5 days was sufficient to significantly reduce mortality even when treatment was delayed 24 h postinoculation. Viral replication in liver, spleen, and kidney, but not lung, of CV-or VV-infected mice was reduced by ST-246 compared to levels for vehicle-treated mice. When 100 mg/kg of ST-246 was given once daily to mice infected by the intranasal route with ECTV, treatment for 10 days prevented mortality even when treatment was delayed up to 72 h after viral inoculation. Viral replication in target organs of ECTV-infected mice was also reduced.National preparedness for bioterrorist events includes the development of rapid detection techniques, improved vaccination strategies, and antimicrobial chemotherapeutics with differing modes of action or targets. Preparing for a weaponized variola virus release is one component necessary for national security, and the development of highly effective, nontoxic antiviral agents that have proven efficacy when given postexposure is essential. Although cidofovir (CDV) has been approved under investigational new drug application for treatment of smallpox or complications of vaccination, its use would be limited since it is not orally bioavailable and produces nephrotoxicity.Previous evaluation of ST-246 for activity against orthopoxviruses has shown both in vitro and in vivo efficacies (13). When evaluated in vitro against vaccinia virus (VV), cowpox virus (CV), ectromelia virus (ECTV), monkeypox virus, camelpox virus, and variola virus, ST-246 inhibited virus replication by 50% at a concentration (50% effective concentration [EC 50 ]) of Յ0.07 M. In animal models using lethal infections with ECTV or VV, ST-246 was reported to be nontoxic and effective against mortality when given orally twice daily at 50 mg/kg of body weight for 14 days beginning before or shortly after infection. ST-246 was also evaluated in the nonlethal mouse tail lesion model by use of intravenous VV to mimic the primary viremic phase of viral infection and systemic lesional disease. When ST-246 was administered by oral gavage at 15 or 50 mg/kg twice daily for 5 days, the tail lesions were significantly reduced (13).The current studies expand upon the previous in vitro and in vivo findings and furt...

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