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Influence of BVDV nonstructural proteins Npro and NS4B on virulence in experimental acutely infected calves

Jamie N Henningson, University of Nebraska - Lincoln

Abstract

Bovine viral diarrhea virus (BVDV) causes significant economic loss in the cattle industry. The open reading frame of BVDV is translated into a polyprotein with viral proteins arranged in the following order: Npro, C, Erns, E1, E2, p7, NS2-3, (NS2), (NS3), NS4A, NS4B, NS5A, and NS5B. The virus exists in two biotypes, noncytopathic (ncp) or cytopathic (cp), based on its effects in cell culture. Npro and NS4B may play a role in host innate immune system evasion and cytopathogenicity, respectively. ^ Npro, a terminal autoprotease, inhibits type I interferon response in cultured cells. Inactivation or deletion of the Npro has resulted in the restoration of type I interferon response in these cultured cells. We examined a pair of noncytopathic viruses, one a variant with a deleted Npro (i-NADL.del (ins)-Δ), and the other the parent virus (i-NADL.del (ins)). Viruses were inoculated intranasally (108 TCID50/ml) into two groups of seronegative calves. Calves given i-NADL.del (ins)-Δ did not show clinical signs, while calves given i-NADL.del (ins) developed a fever with anorexia at days 7 and 8 post inoculation. Both groups of calves experienced a leukopenia and a lymphopenia. Mild lymphoid depletion and antigen deposition was present in Peyer's patches of calves inoculated with i-NADL.del (ins)-Δ as compared to severe lymphoid depletion and antigen deposition present in calves inoculated with i-NADL.del (ins). ^ The mutation of a tyrosine to a cysteine at the position of codon 2441 in the NS4B area of BVDV has been shown to convert a cp virus to a ncp virus in vitro. In this study, a second set of viruses NADL-Y2441C (variant) with the mutation of a tyrosine to a cysteine at position 2441 and ipBSCN-WT (parent) were inoculated intranasally (107 TCID50/ml) into two groups of seronegative calves. The mutation in NADL-Y2441C increased virulence based on development of a leukopenia in calves. This suggests that a biotype switch influenced virulence in the BVDV mutant, NADL-Y2441C. ^

Subject Area

Agriculture, Animal Pathology|Biology, Virology|Biology, Veterinary Science

Recommended Citation

Henningson, Jamie N, "Influence of BVDV nonstructural proteins Npro and NS4B on virulence in experimental acutely infected calves" (2008). ETD collection for University of Nebraska - Lincoln. AAI3321565.
http://digitalcommons.unl.edu/dissertations/AAI3321565

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