Utilization of the prairie dog (Cynomys sp.) animal model for the study of monkeypox virus
Hutson, Christina Leigh
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Since smallpox eradication, monkeypox virus (MPXV) became the most important human health-threat within genus Orthopoxvirus. Previous work demonstrated the prairie dog (PD) MPXV model closely mimics human disease, including development of skin rash. Additionally the model can be used to study pathogenicity differences between the more virulent Congo Basin (CB) MPXV and less virulent West African (WA) MPXV. The goal of this work was to utilize this animal model to further characterize differences in MPXV clade pathogenesis (including apoptosis and NFkB inhibition), and additionally to compare viral pathogenesis/disease presentation in MPXV challenged PDs treated with analgesics. In initial studies, PDs were intranasally infected (8x103p.f.u.) with CB or WA MPXV, and tissues were harvested on subsequent days. Virus was recovered from tissues earlier in CB challenged animals (day 4) than WA challenged animals (day 6). CB MPXV spread more rapidly, accumulated to greater levels, and caused greater morbidity. Further analysis on these tissues was done to determine levels of apoptosis and NFkB activation. In our study, CB MPXV was able to inhibit NFkB in more tissues compared to WA MPXV, but resulted in increased apoptosis. This indicates that circumventing the NFkB pathway may be more important in resulting virulence/pathogenicity than apoptosis inhibition. Additional studies to look at the effect of two common analgesics on MPXV disease progression were done. Understanding whether analgesic agents would affect disease progression is critical when planning animal challenge studies. To investigate this, PDs were challenged with WA MPXV (4X103 pfu) and treated with Metacam (NSAID) or Buprenorphine (opioid). MPXV controls and treatment controls were compared to challenged/treated animals. Disease progression was similar in challenged animals; with the exception of two deaths in the Metacam-treated group. Only subtle differences were seen comparing Buprenorphine-treated MPXV infected animals to controls. Taken together, these findings allow for further characterization of differences between MPXV clade pathogenesis, including identifying early sites during viral replication, cellular response to viral infection and mechanisms the virus uses to evade the immune response. Additionally, we showed that the PD-MPXV model may receive Buprenorphine for short-term pain relief, however NSAIDs should be avoided during challenge studies.