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Published on: September 13, 2018
A High-Potency Bovine Consensus Interferon Delivered by an Oral Lactococcus lactis System Exhibits Antiviral Activity
Hongzhe Zhao1, Rongyan Li1, Yang Yang1
1Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Road, Harbin 150030, China.
Abstract:
Interferon-alpha (IFN-α) mediates innate antiviral immunity. Although it comprises multiple subtypes, their functional divergence and application potential remain incompletely characterized. In this study, we identified 13 BoIFN-α subtypes (A1-A13) in the bovine genome through bioinformatic analysis. Prokaryotic expression and functional comparison revealed substantial differences in antiviral activity among these subtypes (up to 77.7-fold), with BoIFN-A8 being the most potent. Based on these findings, we designed a novel consensus interferon, BoIFN-Acons, by multiple sequence alignment and successfully synthesized it. When expressed in E. coli, BoIFN-Acons exhibited superior antiviral potency (2.36 × 105 U/mg), which was 16.2-fold higher than that of the most active natural subtype. To establish a safe delivery system, we integrated the codon-optimized gene into a food-grade L. lactis expression platform and achieved efficient supernatant production. In vitro assays confirmed that the recombinant BoIFN-Acons effectively suppressed replication of Vesicular stomatitis virus (VSV) and Bovine enterovirus (BEV) and significantly upregulated interferon-stimulated genes (ISGs) such as Mx1 and OAS1. Furthermore, in vivo experiments demonstrated that oral administration of the engineered L. lactis strain alleviated virus-induced clinical symptoms, reduced viral loads in major tissues, and induced upregulation of immune-related genes in the spleen, showing significant prophylactic and therapeutic efficacy. Collectively, this study systematically elucidated the functional diversity of BoIFN-α subtypes and developed a highly active consensus interferon delivered via an oral lactic acid bacteria system, providing a new strategy for the eco-friendly control of animal viral diseases.
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