Modulation of PKR activity in cells infected by bovine viral diarrhea virus.
Bovine viral diarrhea virus is an important animal pathogen. The cytopathic and noncytopathic biotypes of the virus are associated with distinct pathologic entities. A striking difference between the two biotypes is viral RNA accumulation in infected cells. Viral dsRNA is thought to activate protein kinase PKR; an important mediator of innate immunity. In this study, we investigated PKR activation and its consequences in BVDV-infected cells. Infection with cp BVDV was found to induce PKR activation, eIF2alpha phosphorylation, translation inhibition and NF-kappaB activation. In contrast, PKR activity and eIF2alpha phosphorylation were not induced during infection with the ncp BVDV. In addition, cells infected with ncp BVDV showed no PKR phosphorylation in response to infection with the unrelated poliovirus whereas uninfected ncp BVDV cells when infected with poliovirus showed high levels of phosphorylated PKR. Cells infected with ncp BVDV failed to respond to synthetic dsRNA (poly I:C) treatment with NF-kappaB activation. However, the NF-kappaB response to bacterial lipopolysaccarides (LPS) was normal in these cells, suggesting a specific suppression of antiviral response signaling in ncp BVDV infected cells. These results indicate that ncp BVDV has evolved specific mechanisms to prevent activation of PKR and its antiviral effectors, most likely to facilitate the establishment and maintenance of persistent infection.
Gil
Laura H V G
LH
Department of Veterinary and Biomedical Sciences, University of Nebraska-Lincoln, 68583-0905, USA.
van Olphen
Alberto L
AL
Mittal
Suresh K
SK
Donis
Ruben O
RO
D000818:Animals; D019677:Artificial Gene Fusion; D015153:Blotting, Western; D002417:Cattle; D002460:Cell Line; D001908:Diarrhea Viruses, Bovine Viral / Q000502:physiology*; D004789:Enzyme Activation; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D017930:Genes, Reporter; D008156:Luciferases / Q000235:genetics; D008954:Models, Biological; D016328:NF-kappa B / Q000096:biosynthesis; D010766:Phosphorylation; D014176:Protein Biosynthesis; D012330:RNA, Double-Stranded; D019892:eIF-2 Kinase / Q000378:metabolism*
D015852:Eukaryotic Initiation Factor-2; D016328:NF-kappa B; D012330:RNA, Double-Stranded; D008156:Luciferases; D019892:eIF-2 Kinase