Bovine viral diarrhea virus 2 infection induces antiviral and remodeling transcriptional programs in the calf thymus

Authors: VICOSA BAUERMANN, FERNANDO - Oklahoma State University; MERCHIORATTO, INGRYD - Oklahoma State University; Ma, Hao; MENDES PETER, CRISTINA - Oklahoma State University; FALKENBERG, SHOLLIE - Auburn University; RUDD, JENNIFER - Oklahoma State University; NOBRE DA FONSECA, RENATA - Oklahoma State University; GILLIAM, JOHN - Auburn University; TAYLOR, JARED - Oklahoma State University; FERNANDA MAGGIOLI, MAYARA - Oklahoma State University

Submitted to: Veterinary Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/20/2026
Publication Date: 8/31/2026
Citation: Vicosa Bauermann, F., Merchioratto, I., Ma, H., Mendes Peter, C., Falkenberg, S., Rudd, J.M., Nobre Da Fonseca, R., Gilliam, J., Taylor, J., Fernanda Maggioli, M. 2026. Bovine viral diarrhea virus 2 infection induces antiviral and remodeling transcriptional programs in the calf thymus. Veterinary Microbiology. 321. Article 111201. https://doi.org/10.1016/j.vetmic.2026.111201.
DOI: https://doi.org/10.1016/j.vetmic.2026.111201

Interpretive Summary: Bovine Viral Diarrhea Virus (BVDV) infection has been known to decrease calve’s lymphoid tissue, which related to the host’s ability to fight against the virus. Previous research has indicated that thymic regeneration post-BVDV occurs in most animals; however, a significant portion of infected calves display prolonged thymus atrophy. This study provides novel insights into the BVDV-induced thymic immune modulation and tissue adaptation. Our samples also included Influenza D Virus (IDV) -infected animals, whether or not they had been previously infected with BVDV. Post-acute BVDV infection (13 days post-infection, BVDV13) and RNA sequencing of thymus samples indicated a strong anti-viral local immune response, with 251 up-regulated and 44 down-regulated gene transcripts, which associated with T-cell recruitment. By 42 days post-infection (BVDV42+IDV21), in most animals, RNA-sequencing exhibited hallmarks of structural recovery in the thymus, with up-regulation of genes involved in tissue remodeling and extracellular matrix integrity, suggesting a shift toward immune restoration and homeostasis. However, subgroup analysis revealed differences between regenerating and non-regenerating calves. Gene expressions higher in atrophy calves were related to adhesion, angiogenesis, and interferon, whereas genes expressions higher in recovery ones associated with DNA repair, mitochondrial metabolism, survival, and cytoskeletal regulators. These findings suggest that individual variability in immune resilience may influence long-term recovery outcomes. In contrast, IDV exhibited a minimal impact on the transcription of the genes in thymus, with few differentially expressed genes at 21 days post-infection. This indicates that any early immune response to IDV had largely resolved by the time of sampling, reinforcing its role as a respiratory-restricted pathogen with limited systemic involvement. These findings provide a valuable foundation for understanding BVDV-driven immune adaptation and highlight potential targets for enhancing immune resilience and recovery in livestock.

Technical Abstract: Bovine viral diarrhea virus (BVDV) has marked tropism for lymphoid tissues and is associated with thymic atrophy and immune dysfunction in calves. However, the transcriptional programs associated with thymic injury and longer-term recovery remain incompletely defined. To characterize these responses, thymus transcriptomes were profiled by RNA sequencing following experimental BVDV-2 infection, with sampling during the post-acute phase at 13 days post-inoculation (pi) and at a later time (day 42 pi). This transcriptomic analysis was performed in the same calf cohort previously shown to develop variable long-term thymic atrophy and impaired IDV-specific cell-mediated responses after prior BVDV exposure. Post-acute BVDV exposure was associated with a strong thymic immune and antiviral transcriptional signature, with 295 differentially expressed transcripts relative to controls, including prominent chemokine, complement, and antigen-presentation-associated signals. At day 42 pi, relatively few transcripts differed in the broad comparison group, indicating attenuation of the early transcriptional response. In contrast, marked heterogeneity was evident among BVDV-exposed calves, with persistent thymic atrophy versus apparent recovery. Persistent thymic atrophy was associated with enrichment of cell-cycle, chromosome-organization, DNA metabolic, and extracellular-matrix-related programs. Targeted RT-qPCR analysis supported selected extracellular-matrix, spindle/cell-cycle, and lymphoid-development-associated expression differences between calves with persistent thymic atrophy and calves with apparent recovery. The day-42 thymic outcome analysis was exploratory because it involved a small subgroup of calves with persistent atrophy versus apparent recovery. Together, these findings provide a molecular context for the previously observed association between persistent thymic atrophy and weaker T-cell responses to subsequent IDV challenge.