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in Journal of the American Veterinary Medical Association

Abstract

Objective—To characterize the influence of the viral protein Npro 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 Npro-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 Npro 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 Npro-deleted BVDV mutant may represent a safe noncytopathic virus candidate for vaccine development.

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in American Journal of Veterinary Research

Abstract

Objective—To examine the role of bovine viral diarrhea virus (BVDV) biotype on the establishment of fetal infection in cattle.

Animals—30 mixed-breed pregnant cows.

Procedure—Pregnant cows were inoculated oronasally with either i-VVNADL, originating from an infectious BVDV cDNA clone of the National Animal Disease Laboratory (NADL) isolate, or the parental virus stock, termed NADL-A.

Results—All cows developed neutralizing antibodies to BVDV, and virus was commonly isolated from peripheral blood mononuclear cells or nasal swab specimens of NADL-A inoculated cows; however, virus was rarely isolated from specimens of i-VVNADL inoculated cows. i-VVNADL did not cause fetal infection, whereas all fetuses harvested from NADL-A inoculated cows at 6 weeks after inoculation had evidence of infection. Immunoblot analysis of fetal virus isolates revealed the absence of NS3, confirming a noncytopathic (NCP) biotype BVDV in the NADL-A stock. The sequence of the NCP contaminant (termed NADL-1102) and the i-VVNADL genome were virtually identical, with the exception of a 270 nucleotide-long insert in the i-VVNADL genome. Phylogenetic analyses revealed that NADL-1102 forms a monophyletic group with 6 other NADL genomes.

Conclusions and Clinical Relevance—These data suggest that the contaminating NCP virus in the NADL-A stock was the ancestral NADL virus, which originally infected a bovine fetus and recombined to produce a cytopathic (CP) variant. Following oronasal infection of pregnant cows, viremia and transplacental transmission of CP BVDV to the fetus is rare, compared with the high occurrence of maternal viremia and fetal infection observed with NCP BVDV. (Am J Vet Res 2002;63:1455–1463)

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in American Journal of Veterinary Research