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Monkeypox viruses (MPXV) cause human monkeypox, a zoonotic smallpox-like disease endemic to Africa, and are of worldwide public health and biodefense concern. Using viruses from the Congo (MPXV-2003-Congo-358) and West African (MPXV-2003-USA-044) clades, we constructed recombinant viruses that express the luciferase gene (MPXV-Congo/Luc+and MPXV-USA-Luc+) and compared their viral infection in mice by biophotonic imaging. BALB/c mice became infected by both MPXV clades, but they recovered and cleared the infection within 10 days post-infection (PI). However, infection in severe combined immune deficient (SCID) BALB/c mice resulted in 100% lethality. Intraperitoneal (IP) injection of both MPXVCongo and MPXV-Congo/Luc+resulted in a systemic clinical disease and the same mean time-to-death at 9 (±0) days postinfection. Likewise, IP injection of SCID-BALB/c mice with MPXV-USA or the MPXV-USA-Luc+, resulted in similar disease but longer (P<0.05) mean time-to-death (11±0 days) for both viruses compared to the Congo strains. Imaging studies in SCID mice showed luminescence in the abdomen within 24 hours PI with subsequent spread elsewhere. Animals infected with the MPXV-USA/Luc+had less intense luminescence in tissues than those inoculated with MPXV-Congo/Luc+, and systemic spread of the MPXV-USA/Luc+virus occurred approximately two days later than the MPXV-Congo/Luc+. The ovary was an important target for viral replication as evidenced by the high viral titers and immunohistochemistry. These studies demonstrate the suitability of a mouse model and biophotonic imaging to compare the disease progression and tissue tropism of MPX viruses. [ABSTRACT FROM AUTHOR]

Plague is a lethal zoonotic disease associated with rodents worldwide. In the western United States, plague outbreaks can decimate prairie dog (Cynomys spp.) colonies. However, it is unclear where the causative agent, Yersinia pestis, of this flea-borne disease is maintained between outbreaks, and what triggers plague-induced prairie dog die-offs. Less susceptible rodent hosts, such as mice, could serve to maintain the bacterium, transport infectious fleas across a colony, or introduce the pathogen to other colonies, possibly facilitating an outbreak. Here, we assess the potential role of two short-lived rodent species, North American deer mice (Peromyscus maniculatus) and Northern grasshopper mice (Onychomys leucogaster) in plague dynamics on prairie dog colonies. We live-trapped short-lived rodents and collected their fleas on black-tailed (Cynomys ludovicianus, Montana and South Dakota), white-tailed (Cynomys leucurus, Utah and Wyoming), and Utah prairie dog colonies (Cynomys parvidens, Utah) annually, from 2013 to 2016. Plague outbreaks occurred on colonies of all three species. In all study areas, deer mouse abundance was high the year before plague-induced prairie dog die-offs, but mouse abundance per colony was not predictive of plague die-offs in prairie dogs. We did not detect Y. pestis DNA in mouse fleas during prairie dog die-offs, but in three cases we found it beforehand. On one white-tailed prairie dog colony, we detected Y. pestis positive fleas on one grasshopper mouse and several prairie dogs live-trapped 10 days later, months before visible declines and plague-confirmed mortality of prairie dogs. On one black-tailed prairie dog colony, we detected Y. pestis positive fleas on two deer mice 3 months before evidence of plague was detected in prairie dogs or their fleas and also well before a plague-induced die-off. These observations of plague positive fleas on mice could represent early spillover events of Y. pestis from prairie dogs or an unknown reservoir, or possible movement of infectious fleas by mice. [ABSTRACT FROM AUTHOR]