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Influence of BVDV nonstructural proteins Npro and NS4B on virulence in experimental acutely infected calves
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. ^
Agriculture, Animal Pathology|Biology, Virology|Biology, Veterinary Science
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.