Fire-footed rope squirrels (Funisciurus pyrropus) are a reservoir host of monkeypox virus (Orthopoxvirus monkeypox)

Mpox, caused by the monkeypox virus (MPXV; Orthopoxvirus monkeypox ), is on the rise in West and Central Africa. Most outbreaks are short-lived, but MPXV has recently caused larger epidemics driven by sustained human-to-human transmission. It is widely accepted that mpox outbreaks originate in zoonotic events. African rodents, especially squirrels, are suspected to be involved in MPXV emergence, but no formal link to human or nonhuman primate outbreaks has been established. Here, we describe an outbreak of MPXV in a group of wild sooty mangabeys ( Cercocebus atys ) in Taï National Park (Côte d’Ivoire). The outbreak affected one third of the group between January and April 2023, killing four infants. To track its origin, we analysed rodents and wildlife carcasses from the region. We identified a MPXV-infected fire-footed rope squirrel ( Funisciurus pyrropus ), found dead 3 km from the mangabey territory 12 weeks before the outbreak. MPXV genomes from the squirrel and the mangabey were identical. To establish a potential link between these species, we investigated the diet of these mangabeys. We found one video record of consumption of the same squirrel species in 2014. In addition, we performed metabarcoding analyses of faecal samples collected from mangabeys in the four months prior to the outbreak, which identified two faecal samples containing the DNA of the fire-footed rope squirrel. One of these samples was also the first positive for MPXV in the mangabey group. This represents an exceptionally rare case of direct detection of an interspecies transmission event, made possible only by long-term health monitoring. Our findings strongly suggest rope squirrels were the source of the MPXV outbreak in mangabeys. Since squirrels and nonhuman primates are hunted, traded, and consumed by humans in West and Central Africa, exposure to these animals is likely responsible for at least a fraction of human mpox outbreaks.