Objective - To characterize the influence of the viral protein N pro on virulence of bovine viral diarrhea virus (BVDV) and on type I interferon responses in calves. Animals - 10 calves, 4 to 6 months of age. Procedures - BVDV virulence and type I interferon responses of calves (n = 5) infected with a noncytopathic BVDV with a deleted Npro were compared with those of calves (5) infected with a noncytopathic BVDV with a functional Npro. Rectal temperatures, clinical signs, platelet counts, and total and differential WBC counts were evaluted daily. Histologic examinations and immunohistochemical analyses of tissues were conducted to assess lesions and distribution of viral antigens, respectively. Serum type I interferon concentrations were determined. Results - Calves infected with N pro-deleted BVDV developed leukopenia and lymphopenia, without developing increased rectal temperatures or lymphoid depletion of target lymphoid organs. There was minimal antigen deposition in lymphoid organs. Calves infected with Npro BVDV developed increased rectal temperatures, leukopenia, lymphopenia, and lymphoid depletion with marked BVDV antigen deposition in lymphatic tissues. Interferon type I responses were detected in both groups of calves. Conclusions and Clinical Relevance - Deletion of N pro resulted in attenuation of BVDV as evidenced by reduced virulence in calves, compared with BVDV with a functional Npro. Deletion of Npro did not affect induction of type I interferon. The N pro-deleted BVDV mutant may represent a safe noncytopathic virus candidate for vaccine development.
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