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Monkeypox virus (MPXV) is a zoonotic disease endemic in Central and West Africa and is the most virulent orthopoxvirus affecting humans since the eradication of variola virus (VARV). In order to assess their reservoir potential, wild-caught rope squirrels were experimentally infected via intranasal and intradermal exposure with a recombinant MPXV strain from Central Africa engineered to express the luciferase gene. After infection, we monitored viral replication via in vivo bioluminescent imaging and viral shedding via culture and PCR. MPXV infection in African rope squirrels caused mortality and moderate to severe morbidity, with clinical signs including pox lesions in the skin, eyes, mouth and nose, dyspnea, and...


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