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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Ruminant Diseases and Immunology Research » Research » Publications at this Location » Publication #429071

Research Project: Intervention Strategies to Prevent and Control Viral Respiratory Pathogens of Ruminants

Location: Ruminant Diseases and Immunology Research

Title: Bacterially expressed non-glycosylated recombinant bovine interferon lambda demonstrates antiviral activity against bovine viral diarrhea virus in cell culture

Author
item Holthausen, David
item Bickel, Kathryn
item Medina, Gisselle
item Nielsen, Daniel
item Kaplan, Bryan
item Casas, Eduardo
item Dassanayake, Rohana

Submitted to: Research in Veterinary Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/11/2026
Publication Date: N/A
Citation: N/A

Interpretive Summary: Bovine viral diarrhea virus (BVDV) is a major concern in the U.S. cattle industry because it leads to significant economic losses. As a result, developing effective strategies to control BVDV remains a top priority. In our earlier research, we discovered that a natural protein in cows, called interferon lambda, produced using a mammalian (animal) cells in the lab exhibited strong antiviral activity against BVDV. In this new study, we tested the same protein, but this time produced in bacteria instead of animal cells, which is cheaper and simpler to produce. Our results show that this new, bacterially produced version of interferon lambda is still effective against the virus. This finding suggests that its potential use as a cost-effective alternative treatment option for BVDV.

Technical Abstract: Bovine viral diarrhea virus (BVDV) is a pathogen of economic concern for the cattle industry due to reproductive losses, persistently infected animals, and for contributing to the bovine respiratory disease complex. Bovine interferon lambda 3 (IFN-'3) is a type III interferon and a glycosylated cytokine with potent antiviral activity. The recombinant glycosylated bovine IFN-'3 (rbIFN-'3) has antiviral activity against BVDV in Madin-Darby bovine kidney (MDBK) cells. Bacterial expression systems provide a higher-yield and more cost-effective alternative to eukaryotic expression systems. The antiviral properties of bacterially expressed non-glycosylated rbIFN-'3 against BVDV in cell culture was determined in this study. The coding sequence for the mature bovine IFN-'3 was cloned into a bacterial expression vector and non-glycosylated rbIFN-'3 was expressed and purified. Cells were pre-treated with serial dilutions of rbIFN-'3 one day prior to infection with BVDV. The rbIFN-'3 treatment was repeated daily, and viral infection status was assessed three days post-infection using immunohistochemistry with a monoclonal antibody specific to the BVDV E2 glycoprotein. A single band corresponding to non-glycosylated rbIFN-'3 with the expected molecular mass was observed on SDS-PAGE, and the identity of rbIFN-'3 was confirmed via western blotting. Our results indicated that bacterially expressed rbIFN-'3 without glycosylation demonstrated concentration-dependent antiviral activity, effectively reducing BVDV replication. These results indicate that glycosylation is not required for the antiviral function of bovine IFN-'3, and supports the potential of using bacterially expressed, non-glycosylated bovine IFN-'3 in antiviral therapies against BVDV infections.