(869) Comparative analysis of baseline and bovine viral diarrhea virus-induced interferon stimulated gene expression in bovine turbinate and kidney cells
Research Microbiologist USDA/National Animal Disease Center Ankeny, Iowa, United States
Disclosure(s):
David Holthausen, PhD: No financial relationships to disclose
Introduction/Rationale: 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.
