Type 2 BVDV N pro suppresses IFN-1 pathway signaling in bovine cells and augments BRSV replication

• Published in: Virology (New York, N.Y.) Vol. 507; p. 123
• Main Authors: Alkheraif, Abdulrahman A, Topliff, Christina L, Reddy, Jay, Massilamany, Chandirasegaran, Donis, Ruben O, Meyers, Gregor, Eskridge, Kent M, Kelling, Clayton L
• Format: Journal Article
• Language: English
• Published: United States 01-07-2017
• Subjects: Animals; Bovine Virus Diarrhea-Mucosal Disease - genetics; Bovine Virus Diarrhea-Mucosal Disease - metabolism; Bovine Virus Diarrhea-Mucosal Disease - virology; Cattle; Coinfection - genetics; Coinfection - immunology; Coinfection - virology; Diarrhea Virus 2, Bovine Viral - genetics; Diarrhea Virus 2, Bovine Viral - physiology; Interferon-beta - genetics; Interferon-beta - metabolism; NF-kappa B - genetics; NF-kappa B - metabolism; Respiratory Syncytial Virus Infections - genetics; Respiratory Syncytial Virus Infections - immunology; Respiratory Syncytial Virus Infections - veterinary; Respiratory Syncytial Virus Infections - virology; Respiratory Syncytial Virus, Bovine - genetics; Respiratory Syncytial Virus, Bovine - physiology; Signal Transduction; Virus Replication; IFN-1 pathway signaling; mRNA; BRSV; Viral replication; Bovine respiratory disease complex; BVDV2 N(pro)
• ISSN: 1096-0341
• DOI: 10.1016/j.virol.2017.04.015

Bovine viral diarrhea virus (BVDV) infection induces immunosuppression and in conjunction with bovine respiratory syncytial virus (BRSV) contributes to the bovine respiratory disease complex. Bovine turbinate cells were single or co-infected with type 2 BVDV wild-type (BVDV2-wt), its dysfunctional N
mutant (BVDV2-E), and/or BRSV. BVDV2-E significantly up-regulated PKR, IRF-7, TBK-1, IRF-3, and IFN-β mRNAs based on real-time Q-RT-PCR. BRSV-infected cells expressed significantly up-regulated PKR, IRF-3, IRF-7, and IFN-β mRNAs, whereas BVDV2-wt, but not BVDV2-E, abolished this up-regulation in co-infection. No significant differences were observed in MAVS, NF-κB, and PIN-1 mRNAs. A dual-luciferase reporter assay showed that BVDV2-wt significantly increased NF-κB activity compared to BVDV2-E, while BVDV2-E significantly increased IFN-β activity compared to BVDV2-wt. The BRSV titer and RNA levels significantly increased in cells co-infected with BRSV/BVDV2-wt compared to cells co-infected with BRSV/BVDV2-E or infected with BRSV alone. This data supports the synergistic action of BVDV2-wt and BRSV inhibition of IFN-1.