title: Transcriptomic analysis of responses to cytopathic bovine viral diarrhea virus-1 (BVDV-1) infection in MDBK cells.
abstract: The bovine viral diarrhea virus (BVDV) is responsible for significant economic losses in the dairy and cattle industry; however, little is known about the protective and pathological responses of hosts to infection. The present study determined the principal molecular markers implicated in viral infection through meta-transcriptomic analysis using MDBK cells infected for two hours with a field isolate of BVDV-1. While several immune regulator genes were induced, genes involved in cell signaling, metabolic processes, development, and integrity were down-regulated, suggesting an isolation of infected cells from cell-to-cell interactions and responses to external signals. Analysis through RT-qPCR confirmed the expression of more than one hundred markers. Interestingly, there was a significant up-regulation of two negative NF-κB regulators, IER3 and TNFAIP3, indicating a possible blocking of this signaling pathway mediated by BVDV-1 infection. Additionally, several genes involved in the metabolism of reactive oxygen species were down-regulated, suggesting increased oxidative stress. Notably, a number of genes involved in cellular growth and development were also regulated during infection, including MTHFD1L, TGIF1, and Brachyury. Moreover, there was an increased expression of the genes β-catenin, caprin-2, GSK3β, and MMP-7, all of which are crucial to the Wnt signaling pathway that is implicated in the embryonic development of a variety of organisms. This meta-transcriptomic analysis provides the first data towards understanding the infection mechanisms of cytopathic BVDV-1 and the putative molecular relationship between viral and host components.
authors.affiliation: Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Laboratorio de Virología, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Melina
authors.initials: M
authors.lastname: Villalba
authors.affiliation: Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Laboratorio de Virología, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Fredericksen
authors.affiliation: Instituto de Microbiología Clínica, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Carola
authors.initials: C
authors.lastname: Otth
authors.affiliation: Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Laboratorio de Virología, Universidad Austral de Chile, Valdivia, Chile. Electronic address: volavarria@uach.cl.
authors.forename: Víctor
authors.initials: V
authors.lastname: Olavarría
mesh_terms: D000818:Animals; D001912:Bovine Virus Diarrhea-Mucosal Disease / Q000235:genetics* / Q000276:immunology*; D002417:Cattle; D002460:Cell Line; D030241:Diarrhea Virus 1, Bovine Viral; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome
keywords: BVDV-1; Flaviviridae; Meta-transcriptomic; RT-qPCR