One Health Genomic Surveillance at Human–Animal Interfaces in Rural Ghana Reveals Underreported Viruses of Zoonotic and Economic Concern

Under a One Health framework, viruses of veterinary and zoonotic importance pose significant threats to animal and human health, food security, and livelihoods, particularly in regions with intense human–animal interactions. In West Africa, despite recent advances in surveillance programs, important gaps remain in understanding viral diversity and cross-species transmission at wildlife–livestock interfaces. We conducted metagenomic surveillance to characterize viruses circulating across livestock, domestic animals, and wildlife in rural Ghana in 165 animals sampled across five regions. Viral RNA from serum and tissue samples was sequenced with the Illumina platform, and genomes were de novo assembled with MEGAHIT. Phylogenetic relationships were reconstructed using Bayesian approaches. We report the first genomic sequences of porcine parvovirus 3, canine parvovirus, rotavirus A genotype R16, and bovine hepacivirus subtype B from Ghana in over a decade. Phylogenetic analyses revealed intercontinental linkages between Africa and Europe for parvoviruses, persistence of hepacivirus lineages, and evidence of cross-species transmission for rotavirus. Notably, detection in apparently healthy animals highlights underrecognized circulation, gaps in vaccination effectiveness, trade-related biosecurity vulnerabilities, and the role of wildlife in viral maintenance and transmission. Our findings reveal dynamic viral diversity and connectivity across animal populations and ecological interfaces, emphasizing the fluid and interconnected nature of pathogen circulation within One Health systems. By integrating metagenomics and phylogenetics, this study provides a scalable framework for enhancing surveillance capacity, enabling the early detection of emerging threats and informing targeted strategies to mitigate zoonotic and economically important viral diseases in West Africa.