Co-expression of bovine leukemia virus and bovine foamy virus-derived miRNAs in naturally infected cattle

Among the viruses that encode microRNAs (miRNAs) and infect cattle, such as bovine leukemia virus (BLV), bovine foamy virus (BFV), and Bovine herpesviruses, BLV has gained attention due to the critical role that BLV-miRNAs play in inducing lymphosarcoma in infected animals. BLV is highly prevalent in the Americas and negatively affects dairy herds, primarily due to restrictions on the commercialization of dairy products from infected animals and a decrease in milk production. Co-infections involving BLV and BFV appear to be common in cattle. Considering the ability of foamy viruses to cross species barriers, preventing their presence within the food chain is essential. We identified the co-expression of seven BLV-derived miRNAs (blv-miR-B1-3p, blv-miR-B2-5p, blv-miR-B2-3p, blv-miR-B3-5p, blv-miR-B3-3p, blv-miR-B4-3p, and blv-miR-B5-5p) and three BFV-derived miRNAs (bfv-miR-BF1-5p, bfv-miR-BF1-3p, and bfv-miR-BF2-5p) in naturally BLV-infected cows. Besides, seven differentially expressed bovine miRNAs (bta-miR-375, bta-miR-133a, bta-miR-677, bta-miR-1, bta-miR-3613a, bta-miR-9-5p, and bta-miR-95) were identified between cows with high BLV proviral load and uninfected counterparts (|fold change| > 1.5 and q -value < 0.05). A comprehensive analysis of protein-protein interaction networks for genes targeted by viral and host-derived miRNAs suggests a functional convergence on key pathways related to immune response, tumorigenesis, and chromatin remodeling. Although BLV- and BFV-derived miRNAs target different genes, these targets participate in shared biological processes. This convergence might reflect a coordinated viral influence on host functions, with implications for disease progression and the increased dissemination of BFV. These findings offer new perspectives for creating diagnostic and treatment approaches to manage viral persistence and tumorigenesis in cattle.

IMPORTANCE

The bovine leukemia virus (BLV) and bovine foamy virus (BFV) are retroviruses that encode microRNAs (miRNAs) and infect cattle. While the role of BFV-derived miRNAs remains unclear, BLV miRNAs have gained attention for their potential involvement in oncogenesis. BLV-BFV co-infections are common, and given foamy viruses’ potential to cross species barriers, it is essential to prevent their presence in the food chain. We reported the co-expression of three BFV-derived miRNAs and seven BLV-derived miRNAs in naturally infected cattle. A protein-protein interaction graph analysis of genes targeted by viral and host-derived miRNAs revealed key metabolic pathways associated with tumorigenesis, immune response regulation, and chromatin remodeling. Although BLV- and BFV-derived miRNAs target different genes, these targets participate in shared biological processes, suggesting a functional convergence that may influence disease progression and BFV dissemination. These findings offer opportunities for developing diagnostic and therapeutic strategies to control viral persistence and tumor development in cattle.