Abstract
<title>Abstract</title> <p> We report the first detection and genomic characterization of Porcine Parvovirus 6 (PPV6) ( <italic>Copiparvovirus ungulate4</italic> ) in Africa, identified in a pig from Nigeria in 2021. Metagenomic sequencing of spleen tissue revealed a novel PPV6 variant (designated NGRA4) belonging to the genus <italic>Copiparvovirus</italic> . Phylogenetic analysis of coding-complete genomes demonstrated that NGRA4 forms a distinct lineage that is ancestral to previously reported PPV6 variants globally. The NS1 protein exhibited 96.8% amino acid similarity to its closest relative in GenBank and contained 22 amino acid substitutions, half of which were in the helicase and origin-binding domains. Structural modeling of the capsid protein identified three domains, separated by polyglycine tracts and designated here as domains A, B and C (D-A, D-B, and D-C). D-A appeared to be the most rapidly evolving region, whereas D-B and D-C showed structural similarity to phospholipase A2 and parvovirus capsid proteins, respectively. Three surface-exposed amino acid substitutions in the D-C region (cluster X: A790P, T798S, and T931N) mapped to predicted B-cell epitopes and spatially overlapped with neutralizing antibody binding sites identified in the capsid of parvovirus B19 (pdb id: 6nn3), suggesting immune-driven evolution. Capsid structure prediction suggests a unique feature that bridges adjacent three-fold axes through the two-fold axis. Collectively, our findings suggest NGRA4 is a highly divergent PPV6 lineage that is under immunological pressure and detected for the first time in Nigeria and Africa. The distinctive genetic, immunologic and structural features of NGRA4 highlight the need for enhanced surveillance of PPV6 in African swine populations to better understand its epidemiology, potential role in reproductive failure and organ pathology, and implications for future control strategies. </p>