Abstract
BACKGROUND: A significant number of infectious diseases affecting humans have been associated with zoonotic viruses. Wild small mammals, such as bats, rodents, and shrews, serve as natural reservoirs for a multitude of zoonotic viruses, particularly in Africa, where zoonosis is prevalent. Nevertheless, our knowledge of the virome composition within these hosts remains limited, impeding a more profound understanding of spillover events into human populations. RESULTS: We employed a viral metagenomics approach to characterize the virome in 846 wild small mammals sampled from Sierra Leone. Based on the complete RNA-dependent RNA polymerase genome, a total of 39 RNA viruses infecting mammals were identified, comprising 13 known viruses and 26 novel viruses. Notably, the Paramyxoviridae family exhibited the highest diversity of viral species across all three orders of wild mammal. The animal species Hipposideros jonesi and Lophuromys chrysopus were found to harbor the highest viral richness. Among these viral species, 15 were identified as cross-species transmitted viruses shared among different animal species, 3 were classified as zoonotic (Encephalomyocarditis virus, Rocahepevirus sp., and Lassa virus), while 3 others posed a potential risk for spillover (melian virus, Rodent hepacivirus, Hunnivirus A). Cross-species transmission analysis revealed that rodents played central roles in virus sharing, while cross-order viral transmission was less likely to occur in bats. Among 26 newly identified viruses, four viruses (Bat ledantevirus 2, Rattus rattus jeilongvirus, Miniopterus inflatus ribovirus, and Rat mamastrovirus) were predicted to have high zoonotic potential. Among them, Bat ledantevirus 2 exhibited the highest zoonotic potential and phylogenetic relatedness to the known human-infecting virus (Le Dantec virus). Further seroepidemiological analysis in patients, using single-round infectious virus particles as antigens, revealed the presence of neutralizing antibodies against Bat ledantevirus 2, a novel virus belonging to the Rhabdoviridae family. CONCLUSIONS: These findings highlight the critical need for enhanced surveillance at the human-animal interface in order to identify viruses with cross-species transmission potential prior to their spillover into human population. Video Abstract.