Mpox (MPXV) is a zoonotic orthopoxvirus that has re-emerged as a global public health concern after declarations of Public Health Emergencies of International Concern by the World Health Organization in 2022 and 2024. Recent outbreaks have highlighted sustained human-to-human transmission, specifically through close-contact networks. Genomic surveillance in Central and West Africa indicates that much of MPXV diversity arises from repeated zoonotic spillover events. To detect the natural reservoir(s) of MPXV is important to understand viral maintenance in wild and prevent future outbreaks. Although several African rodents, specifically rope squirrels, have long been suspected as potential reservoirs, definitive evidence of their role in maintaining and transmitting the virus has remained limited.
The aim of this study was to determine the likely source of the 2023 MPXV outbreak in a habituated group of sooty mangabeys and to assess whether fire-footed rope squirrels act as natural hosts and potential reservoirs of the virus. The researchers also aimed to assess how MPXV circulated in wildlife species in TNP and to assess spillover risks in humans and primates, specifically in the context of bushmeat hunting and habitat overlap.
The researchers implemented a comprehensive and multidisciplinary approach, integrating wildlife health monitoring, ecological investigation, molecular diagnostics, viral genome sequencing, and phylogenetic analysis. The mangabey group, which consists of about 80 individuals, was closely monitored as part of a long-term veterinary surveillance program. Faecal samples were collected longitudinally before, during, and after the outbreak. Necropsies were performed on deceased animals using strict biosafety protocols. A total of 444 faecal samples from mangabeys were tested for MPXV by using quantitative PCR targeting viral genes.
Extensive trapping and sampling of rodents and shrews were conducted inside and around TNP from 2019 to 2024. Over 1,000 tissue and swab samples from small mammals were screened for orthopoxviruses, with positive samples further tested specifically for MPXV. Virus isolation was attempted in cell culture, and high-throughput sequencing with hybridization capture techniques was used to assemble near-complete viral genomes. Phylogenetic analyses were performed by using maximum-likelihood and Bayesian molecular clock models to evaluate evolutionary relationships and divergence times.
Dietary metabarcoding of mangabey faecal samples was performed to detect prey DNA and investigate possible predator–prey transmission pathways. Earlier published carrion fly metabarcoding data were reanalysed to assess the ecological distribution of potential reservoir species across habitat gradients ranging from pristine forest to villages.
The 2023 outbreak analysis found that 32.5% of the 80 mangabeys developed MPXV-related skin lesions, with four infant fatalities. MPXV DNA was detected in 36 fecal samples from 19 mangabeys, indicating significant subclinical transmission. A fire-footed rope squirrel found dead 12 weeks earlier tested positive for MPXV. Its genome closely matched that of the mangabey virus, which indicates recent cross-species transmission. Early fecal samples from December 2022 exhibited asymptomatic MPXV shedding and contained squirrel DNA. This supports predator-prey transmission as a spillover event. Ecological assessments indicated that fire-footed rope squirrels, commonly found in hunted areas, present zoonotic transmission risks. Genomic comparisons also showed considerable strain diversity in Côte d’Ivoire, which reflects complex viral circulation among host species.
Overall, the findings suggest that fire-footed rope squirrels may serve as natural hosts of MPXV and could transmit the virus to wild primates in TaĂŻ National Park. The evidence supports cross-species transmission through hunting and consumption. The researchers emphasize the multi-host ecology of MPXV and the potential risk of exposure to humans from both rodents and infected primates. Effective prevention strategies must include enhanced wildlife surveillance, genomic monitoring, ecological research, and interventions addressing bushmeat hunting to mitigate spillover risks and decrease the threat posed by this zoonotic virus.
Reference: Riutord-Fe C, Schlotterbeck J, Lagostina L, et al. Transmission of MPXV from fire-footed rope squirrels to sooty mangabeys. Nature. 2026. doi:10.1038/s41586-025-10086-y
