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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Virus and Prion Research » Research » Publications at this Location » Publication #181510

Title: MODULATION OF CELLULAR SIGNALING PATHWAYS HIGHLY DEPENDS ON VIRULENCE AND CYTOPATHOGENIC PHENOTYPES OF BOVINE VIRAL DIARRHEA VIRUSES TYPE 2

Author
item BENDFELDT, STEFANIE - UNIV VET MED, HANNOVER
item Neill, John
item Ridpath, Julia

Submitted to: Ruminant Pestiviruses Symposium Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 9/14/2005
Publication Date: 9/14/2005
Citation: Bendfeldt, S., Neill, J.D., Ridpath, J.F. 2005. Modulation of cellular signaling pathways highly depends on virulence and cytopathogenic phenotypes of bovine viral diarrhea viruses type 2 [abstract]. 6th Pestiviruses Symposium. Paper No. T2-1. p. 30.

Interpretive Summary:

Technical Abstract: Modulation of host cell signaling pathways is a crucial step for efficient virus replication and virus release. Different bovine viral diarrhea virus (BVDV) isolates may have evolved different strategies. These differences might explain the variation in severity of clinical disease observed following BVDV infection. Clinical presentation may range from subclinical to clinically severe (severe acute BVD or sa BVD). Sa BVD is caused by certain BVDV2 strains. Based on their activity in cultured epithelial cells they segregate into the noncytopathic BVDV genotype. In contrast to noncytopathic strains that do not cause sa BVD, infection of bovine lymphosarcoma cells (BL3) with sa BVD associated ncp BVDV2 results in massive cell death. To understand the impact of an infection with highly virulent ncp BVDV2, we analyzed the involvement of different cell signaling pathways. Using FACS analysis, fluorescence microscopy and phospho-specific antibodies we demonstrated that the PI3 K/Akt survival pathway is activated after infection with highly virulent ncp BVDV2 while the stress mediated p38 MAPK pathway was not. Moreover, NF'B was translocated to the nucleus leading to stress-induced gene regulation. The kinase Mnk1, which is activated by two different pathways, is phosphorylated after infection, regardless of BVDV2 biotype and virulence. Our results indicate that highly virulent ncp BVDV2 influence the antiviral response of the infected cell in a different manner than less virulent BVDV2 which may explain the outcome of sa BVD.