Antiviral activity of bovine type III interferon against bovine viral diarrhea virus is greatly reduced in bovine turbinate cells due to limited expression of IFN lambda receptor 1 (IL-28Rα).

Autor: Dassanayake RP; Ruminant Diseases and Immunology Research Unit, Agricultural Research Service, National Animal Disease Center, United States Department of Agriculture, Ames, IA, United States., Menghwar H; Ruminant Diseases and Immunology Research Unit, Agricultural Research Service, National Animal Disease Center, United States Department of Agriculture, Ames, IA, United States.; ARS Research Participation Program, Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN, United States., Bickel KA; Ruminant Diseases and Immunology Research Unit, Agricultural Research Service, National Animal Disease Center, United States Department of Agriculture, Ames, IA, United States., Holthausen DJ; Ruminant Diseases and Immunology Research Unit, Agricultural Research Service, National Animal Disease Center, United States Department of Agriculture, Ames, IA, United States., Ma H; Ruminant Diseases and Immunology Research Unit, Agricultural Research Service, National Animal Disease Center, United States Department of Agriculture, Ames, IA, United States., Diaz-San Segunda F; Plum Island Animal Disease Center, North Atlantic Area, Agricultural Research Service, United States Department of Agriculture, Greenport, NY, United States., Rodriguez-Calzada M; Plum Island Animal Disease Center, North Atlantic Area, Agricultural Research Service, United States Department of Agriculture, Greenport, NY, United States., Medina GN; Plum Island Animal Disease Center, North Atlantic Area, Agricultural Research Service, United States Department of Agriculture, Greenport, NY, United States.; National Bio and Agro-Defense Facility (NBAF), ARS, USDA, Manhattan, KS, United States., Attreed S; Plum Island Animal Disease Center, North Atlantic Area, Agricultural Research Service, United States Department of Agriculture, Greenport, NY, United States., Falkenberg SM; Sugg Laboratory, Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, United States., Kanipe C; Bacterial Diseases of Livestock Research Unit, National Animal Disease Center, Agricultural Research Service, USDA, Ames, IA, United States., Sacco RE; Ruminant Diseases and Immunology Research Unit, Agricultural Research Service, National Animal Disease Center, United States Department of Agriculture, Ames, IA, United States., De Los Santos T; Plum Island Animal Disease Center, North Atlantic Area, Agricultural Research Service, United States Department of Agriculture, Greenport, NY, United States., Casas E; Ruminant Diseases and Immunology Research Unit, Agricultural Research Service, National Animal Disease Center, United States Department of Agriculture, Ames, IA, United States.
Jazyk: angličtina
Zdroj: Frontiers in immunology [Front Immunol] 2024 Aug 19; Vol. 15, pp. 1441908. Date of Electronic Publication: 2024 Aug 19 (Print Publication: 2024).
DOI: 10.3389/fimmu.2024.1441908
Abstrakt: Introduction: The antiviral activity of recombinant bovine interferon lambda 3 (bovIFN-λ3) against bovine viral diarrhea virus (BVDV) has been demonstrated in vitro in Madin-Darby bovine kidney cells (MDBK) and in vivo in cattle. However, anti-BVDV activity of bovIFN-λ3 has not been studied in bovine respiratory tract epithelial cells, supposedly a primary target of BVDV infection when entering the host by the oronasal route.
Methods: Here we investigated the anti-BVDV activity of bovIFN-λ3 in bovine turbinate-derived primary epithelial cells (BTu) using BVDV infection and immunoperoxidase staining, TCID 50 , RT-qPCR, DNA and transcriptome sequencing, and transfection with plasmids containing the two subunits, IL-28Rα and IL-10Rβ that constitute the bovIFN-λ3 receptor.
Results: Our immunoperoxidase staining, RT-qPCR, and TCID 50 results show that while BVDV was successfully cleared in MDBK cells treated with bovIFN-λ3 and bovIFN-α, only the latter, bovIFN-α, cleared BVDV in BTu cells. Preincubation of MDBK cells with bovIFN-λ3 before BVDV infection was needed to induce optimal antiviral state. Both cell types displayed intact type I and III IFN signaling pathways and expressed similar levels of IL-10Rβ subunit of the type III IFN receptor. Sequencing of PCR amplicon of the IL-28Rα subunit revealed intact transmembrane domain and lack of single nucleotide polymorphisms (SNPs) in BTu cells. However, RT-qPCR and transcriptomic analyses showed a lower expression of IL-28Rα transcripts in BTu cells as compared to MDBK cells. Interestingly, transfection of BTu cells with a plasmid encoding IL-28Rα subunit, but not IL-10Rβ subunit, established the bovIFN-λ3 sensitivity showing similar anti-BVDV activity to the response in MDBK cells.
Conclusion: Our results demonstrate that the sensitivity of cells to bovIFN-λ3 depends not only on the quality but also of the quantity of the IL-28Rα subunit of the heterodimeric receptor. A reduction in IL-28Rα transcript expression was detected in BTu as compared to MDBK cells, despite the absence of spliced variants or SNPs. The establishment of bovIFN-λ3 induced anti-BVDV activity in BTu cells transfected with an IL-28Rα plasmid suggests that the level of expression of this receptor subunit is crucial for the specific antiviral activity of type III IFN in these cells.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
(Copyright © 2024 Dassanayake, Menghwar, Bickel, Holthausen, Ma, Diaz-San Segunda, Rodriguez-Calzada, Medina, Attreed, Falkenberg, Kanipe, Sacco, De Los Santos and Casas.)
Databáze: MEDLINE
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