LAUSR

Background Previous human cases or epidemics have suggested that Monkeypox virus (MPXV) can be transmitted through contacts with animals of African rainforests. Although MPXV has been identified in many mammal species, most are likely secondary hosts and the reservoir host has yet to be discovered. Methodology/Principal Findings In this study, we provide the full list of African mammal genera (and species) in which MPXV was previously detected and predict the geographic distributions of all species of these genera based on museum specimens and an ecological niche modelling (ENM) method. Then, we reconstruct the ecological niche of MPXV using georeferenced data on animal MPXV sequences and human index cases, and conduct overlap analyses with the ecological niches inferred for 99 mammal species in order to identify the most probable animal reservoir. Conclusions/Significance Our results show that the MPXV niche covers three African rainforests, the Congo Basin and Upper and Lower Guinean forests. The four mammal species showing the best niche overlap with MPXV are all arboreal rodents, including three squirrels, Funisciurus anerythrus, Funisciurus pyrropus, and Heliosciurus rufobrachium, and Graphiurus lorraineus. We conclude that the most probable MPXV reservoir is F. anerythrus based on two niche overlap metrics, the areas of higher probabilities of occurrence, and available data on MPXV detection. Summary Monkeypox (MPX) is an emerging zoonotic disease, endemic to rainforests of West and Central Africa, which manifests as a fever, swollen lymph nodes, and fatigue, followed by a rash with macular lesions progressing from papules to vesicles, pustules and scabs, usually on the face, hands, and feet for two to four weeks. The case fatality rate ranges from 1-3% in West Africa to 5-10% in Central Africa. The disease has been reported in 10 African countries between 1970 and today, with an increasing number of cases over the last decades and several exportations outside the continent, the last one in 2022 resulting in an epidemic involving mostly men who have sex with men, with more than 80,000 cases detected worldwide. Although MPX virus has been identified in many mammal species, most are likely secondary hosts and the reservoir host has yet to be discovered. In this study, we compare the predicted geographic distribution (ecological niche) of the MPX virus with that of 99 mammal species, and conclude that the most probable MPX reservoir is Thomas’s rope squirrel (Funisciurus anerythrus), followed by three other arboreal rodents, including two squirrels (Funisciurus pyrropus and Heliosciurus rufobrachium) and the Lorrain dormouse (Graphiurus lorraineus).