Cytopathic BVDV-1 strain induces immune marker production in bovine cells through the NF-κB signaling pathway.
The bovine viral diarrhea virus (BVDV-1) is a pathogen responsible for high economic losses in the cattle industry worldwide. This virus has the capacity to modulate the immune system of several higher vertebrates, but there is little information available on the cell infection mechanism. To further investigate the effects of BVDV-1 on the activation of the immune response, the Madin-Darby bovine kidney cell line was infected with the cytopathic CH001 field isolate of BVDV-1, and the proinflammatory and antiviral cytokine expression profiles were analyzed. The results showed that BVDV-1 was able to induce the production of BCL3, IL-1β, IL-8, IL-15, IL-18, Mx-1, IRF-1, and IRF-7 in a way similar to polyinosinic-polycytidylic acid. Interestingly, all BVDV-1 activities were blocked by pharmacological inhibitors of the NF-κB signaling pathway. These results, together with in silico analyses showing the presence of several regulatory consensus target motifs, suggest that BVDV-1 regulates gene expression in bovines through the activation of several key transcription factors. Collectively, these data identified BVDV-1 as a viral regulator of immune marker expression, even from early infection. Additionally, this is the first report to find BVDV-1 modulating the activation of cytokine production and transcriptions factors mainly through the NF-κB pathway in vertebrates.
Facultad de Ciencias, Instituto de Bioquímica y Microbiología, Universidad Austral de Chile, Campus Isla Teja S/N, Valdivia, Chile.
Fernanda
F
Fredericksen
Facultad de Ciencias, Instituto de Bioquímica y Microbiología, Universidad Austral de Chile, Campus Isla Teja S/N, Valdivia, Chile.
Gonzalo
G
Carrasco
Facultad de Ciencias, Instituto de Bioquímica y Microbiología, Universidad Austral de Chile, Campus Isla Teja S/N, Valdivia, Chile.
Melina
M
Villalba
Facultad de Ciencias, Instituto de Bioquímica y Microbiología, Universidad Austral de Chile, Campus Isla Teja S/N, Valdivia, Chile. Electronic address: volavarria@uach.cl.
Víctor H
VH
Olavarría
D000818:Animals; D000081242:B-Cell Lymphoma 3 Protein; D015415:Biomarkers / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D001908:Diarrhea Viruses, Bovine Viral / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000821:virology; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000276:immunology; D050839:Interferon Regulatory Factor-7 / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D064547:Myxovirus Resistance Proteins / Q000235:genetics / Q000276:immunology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D009570:Nitriles / Q000494:pharmacology*; D011070:Poly I-C / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D013450:Sulfones / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology
D000081242:B-Cell Lymphoma 3 Protein; C416282:BAY 11-7085; D015415:Biomarkers; D050856:Interferon Regulatory Factor-1; D050839:Interferon Regulatory Factor-7; D007378:Interleukins; D064547:Myxovirus Resistance Proteins; D016328:NF-kappa B; D009570:Nitriles; D011518:Proto-Oncogene Proteins; D013450:Sulfones; D014157:Transcription Factors; D011070:Poly I-C
BVDV-1; Immune marker; NF-κB