Hepatitis C virus (HCV; genus Hepacivirus) represents a major public health problem, infecting about three per cent of the human population. Because no animal reservoir carrying closely related hepaciviruses has been identified, the zoonotic origins of HCV still remain unresolved. Motivated by recent findings of divergent hepaciviruses in rodents and a plausible African origin of HCV genotypes, we have screened a large collection of small mammals samples from seven sub-Saharan African countries. Out of 4,303 samples screened, eighty were found positive for the presence of hepaciviruses in twenty-nine different host species. We, here, report fifty-six novel genomes that considerably increase the diversity of three divergent rodent hepacivirus lineages. Furthermore, we provide strong evidence for hepacivirus co-infections in rodents, which were exclusively found in four sampled species of brush-furred mice. We also detect evidence of recombination within specific host lineages. Our study expands the available hepacivirus genomic data and contributes insights into the relatively deep evolutionary history of these pathogens in rodents. Overall, our results emphasize the importance of rodents as a potential hepacivirus reservoir and as models for investigating HCV infection dynamics.

Charite Universitatsmedizin Berlin Berlin Germany

Department of Biology and Institute of Mountain Research and Development Mekelle University Mekelle Ethiopia

Department of Biology Evolutionary Ecology Group University of Antwerp Antwerp Belgium

Department of Botany and Zoology Faculty of Science Masaryk University Brno Czech Republic

Department of Ecology and Animal Resource Management Faculty of Science Biodiversity Monitoring Center University of Kisangani Kisangani Democratic Republic of the Congo

Department of Microbiology Immunology and Transplantation Rega Institute KU Leuven Leuven Belgium

Department of Pathobiology and Population Sciences The Royal Veterinary College London UK

Department of Zoology University of Oxford Oxford UK

EcoHealth Alliance New York NY USA

German Center for Infection Research Berlin Germany

Institute of Vertebrate Biology of the Czech Academy of Sciences Brno Czech Republic

OD Taxonomy and Phylogeny Royal Belgian Institute of Natural Sciences Brussels Belgium

Pest Management Center Sokoine University of Agriculture Morogoro Tanzania

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The evolutionary history of hepaciviruses

Phylogenomic Characterization of Lopma Virus and Praja Virus, Two Novel Rodent-Borne Arteriviruses