Transcriptomic analysis reveals that BVDV alters immune and metabolic responses to Brucella abortus A19 in RAW264.7 macrophages

Background The co-occurrence of bovine viral diarrhea virus (BVDV) infection and brucellosis in cattle is common. However, the effect of BVDV-induced immunosuppression on the efficacy of the Brucella abortus ( B. abortus ) A19 vaccine remains unclear. We hypothesized that BVDV infection suppresses the host immune response to the B. abortus A19 vaccine by dysregulating key immune-related genes, thereby potentially affecting vaccine immunoprotection. This study aims to explore the possible mechanism by which BVDV infection may influence the cellular response to the B. abortus A19 vaccine, as revealed by transcriptome sequencing results. Methods To preliminarily assess the impact on immune organs, a mouse model of co-infection with BVDV and B. abortus A19 was established. Pathological sections of the spleen of the mice were prepared to examine the impact of BVDV infection on the immune organs of co-infected mice. Subsequently, to investigate the underlying molecular mechanisms, the RAW264.7 mouse macrophage in vitro model of co-infection with BVDV and B. abortus A19 was constructed, and the comprehensive effect of BVDV on B. abortus A19 in RAW264.7 cells was studied using transcriptome analysis. Results Compared to the control group, B. abortus A19 single infection resulted in 1,926 differentially expressed genes (DEGs), which were enriched in various immune-related signaling pathways. Compared to the B. abortus A19 single infection, the mixed infection group of BVDV and B. abortus A19 identified 4,810 DEGs, which were widely involved in immune, inflammatory, and metabolism-related pathways. There were 1,047 overlapping DEGs between the two DEG groups, of which 922 DEGs had a reverse expression trend and were involved in immune inflammation and cellular metabolism. Conclusion This study reveals that BVDV infection can significantly alter the expression of genes related to immune response, inflammatory response, and cell metabolism in RAW264.7 macrophages. These findings suggest that BVDV may interfere with the cellular response to the B. abortus A19 vaccine in vitro , clarifying potential molecular mechanisms whereby BVDV might affect vaccine-induced immune protection. This provides a theoretical basis for further validation in bovine models and for optimizing vaccination strategies in at-risk cattle populations.