Transcriptomic and Proteomic Approaches Reveal the Biological Functions of Two Novel Porcine-Origin Noncoding DNA Molecules

Porcine circovirus-like mini agents (PCVLs) with small circular noncoding DNA genomes have recently been discovered in animals. Currently, the biological activity of PCVLs remains unclear. In this study, we conducted transcriptomic and proteomic analyses to compare the differential expression of genes and proteins in the livers of PCVL258/PCVL264 molecular clone-infected and mock-infected BALB/c mice at 7 and 28 days postinfection (dpi). Gene Ontology/Kyoto Encyclopedia of Genes and Genomes association analysis of the transcriptome and proteome showed that the differentially expressed genes and proteins (DEGs and DEPs) in the livers of PCVL258-infected mice were predominantly enriched in metabolic, cancer, and neurodegenerative disease signaling pathways. On the other hand, the DEGs and DEPs in the livers of PCVL264-infected mice were principally related to metabolic, reproductive, and pancreatic-associated pathways. We present the first application of transcriptomics combined with proteomics to determine the biological activities of small pathogen-associated DNA molecules, thus providing valuable information for understanding small circular DNA molecules that cannot encode proteins in the generation of specific human diseases.