Profiling the DuCV-1 Cap-associated host interactome by Co-IP/LC-MS: implications for host-response pathways and viral pathogenesis.

Duck circovirus genotype 1 (DuCV-1) infection is a severe immunosuppressive disease that significantly impairs poultry growth. As the sole structural protein and major immunogen of DuCV-1, the capsid protein (Cap) plays a critical role in viral infection and pathogenesis. Elucidating the interactions between Cap and host proteins is essential for revealing the molecular basis of DuCV-1 pathogenicity. In this study, we performed, for the first time, using immunoprecipitation coupled with mass spectrometry (MS) to identify 288 potential host proteins that interact with Cap in Cap-transfected HD11 cells. Integrative analyses of protein-protein interaction (PPI) networks, Gene Ontology (GO) annotation, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment showed that Cap-interacting host proteins are functionally enriched in multiple biological processes, including cytoskeleton remodeling, nucleic acid translation apparatus, endocytic trafficking, autophagy, and innate immune signaling. Further functional enrichment analyses confirmed that these Cap-binding factors are predominantly enriched in pathways associated with cytoskeleton remodeling, protein translation, transcriptional regulation, and DNA damage response. Moreover, we verified the binding of nine candidate Cap-interacting proteins to DuCV-1 Cap, including RB1-inducible coiled-coil 1, Exocyst complex component 1, Tubulin alpha-1A chain, Transcription factor E2F8, Nucleolar and coiled-body phosphoprotein 1, Ubiquitin-protein ligase E3B, DNA repair protein RAD52 homolog, Junction plakoglobin, and Tubulin alpha-1C chain. Collectively, the interactome dataset and network analysis provide new insights into the potential pathogenic mechanisms of DuCV-1.