Characterization of Monkeypox virus infection in African rope squirrels (Funisciurus sp.)

Monkeypox (MPX) is a zoonotic disease endemic in Central and West Africa and is caused by Monkeypox virus (MPXV), the most virulent Orthopoxvirus affecting humans since the eradication of Variola virus (VARV). Many aspects of the MPXV transmission cycle, including the natural host of the virus, remain unknown. African rope squirrels (Funisciurus spp.) are considered potential reservoirs of MPXV, as serosurveillance data in Central Africa has confirmed the circulation of the virus in these rodent species [1,2]. In order to understand the tissue tropism and clinical signs associated with infection with MPXV in these species, 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 and shedding via in vivo bioluminescent imaging, viral culture and real time 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 profuse nasal discharge. Both intranasal and intradermal exposures induced high levels of viremia, fast systemic spread, and long periods of viral shedding. Shedding and luminescence peaked at day 6 post infection and was still detectable after 15 days. Interestingly, one sentinel animal, housed in the same room but in a separate cage, also developed severe MPX disease and was euthanized. This study indicates that MPXV causes significant pathology in African rope squirrels and infected rope squirrels shed large quantities of virus, supporting their role as a potential source of MPXV transmission to humans and other animals in endemic MPX regions.
Author summary Monkeypox virus (MPXV) is a virus closely related to Variola virus, the cause of smallpox, and it causes a similar, though less severe, disease in humans in Central and West Africa. This disease is particularly dangerous for children and people with compromised immune systems and the mortality rate is estimated to be about 10% in the more pathogenic Central African strains. Unlike Variola virus, MPXV is primarily transmitted to humans from animals, but it is not known which species commonly carry and spread this virus. Rope squirrels in the genus Funisciurus have previously been linked to the virus in Central Africa. In this study, rope squirrels were experimentally infected with MPXV and subsequently monitored for signs of disease, as well as the amount of virus they shed in their bodily fluids. The results of this study showed that rope squirrels became moderately ill but not all died. They shed large amounts of virus in oral, nasal, rectal, and ocular secretions. This information helps public health doctors and epidemiologists understand the potential risks of contacting rope squirrels for local populations in Africa and will help disease ecologists understand how MPXV is maintained and transmitted between animals and to humans.