Comparative analysis of baseline and bovine viral diarrhea virus-induced interferon stimulated gene expression in bovine turbinate and kidney cells 2305626

Abstract Introduction Bovine viral diarrhea virus (BVDV) is a significant economic concern for the American cattle industry. Transcriptome analyses of BVDV-infected animals have shown that the virus alters host gene expression, particularly within immune-related pathways. Differences in BVDV-mediated interferon stimulated gene (ISG) expression have not been studied in a controlled cell culture system. This study aims to investigate selected early ISG transcriptome profiles in two bovine cell lines infected with BVDV at different multiplicities of infection (MOI). Methods Madin-Darby bovine kidney epithelial cells (MDBK), and bovine turbinate primary neonatal-derived cells (BTu) were infected with a noncytopathic BVDV1a strain (PI28) at two different MOIs (0.5 and 50) and transcriptomic analysis was completed at 8-, 24-, and 72-hours post-infection. Thirty ISGs were analyzed to compare their baseline and BVDV-induced gene expression across the three timepoints. Results Of the 30 ISGs, 11 have higher baseline transcription in MDBKs: ISG20, IFITM3, RIG-I, USP18, CASP4, CASP8, TRIM21, TRIM14, LGALS3BP, RNASEL, and IFI6. Only 4 ISGs, SOCS3, ALCAM, ICAM1, and CD47 have higher baseline transcription levels in BTus than MDBKs. BVDV infection elicited prolonged 8—24-hour gene expression and increased transcription of RIG-I, Mx1, MDA5, CASP4, CASP8, LGALS3BP, TRIM21, and TRIM14 in MDBK cells in the 50 MOI condition and reduced transcription in the 0.5 MOI condition at 24 hours. In BTus, SOCS3, ALCAM, ICAM1, and CD47 demonstrated BVDV-induced increases with 50 MOI infection and decreases with 0.5 MOI infection at 24 hours. Conclusion BVDV modulates the host innate immune response, as illustrated by the modulation in ISG transcription in vitro. These effects are viral load-dependent, with the low titer infections (0.5 MOI) reducing ISG gene expression below cellular control levels, whereas high titer infections (50 MOI) increase ISG gene expression. Funding Source USDA/Agricultural Research Service, Project 5030-32000-229-000D Topic Categories Veterinary and Comparative Immunology (VET)