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Evaluation of antiviral activity and toxicity of recombinant human interferon alfa-2a in calves persistently infected with type 1 bovine viral diarrhea virus

Simon F. PeekDepartment of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

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 BVSc, PhD
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Michael D. BondsDepartment of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

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Patrick SchaeleDepartment of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

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Sarah WeberDepartment of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

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Kristin FriedrichsDepartment of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

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Ronald D. SchultzDepartment of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

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 PhD

Abstract

Objective—To evaluate antiviral activity and toxicity of recombinant human interferon alfa-2a in calves persistently infected with noncytopathic type 1 bovine viral diarrhea virus (BVDV).

Animals—5 Holstein heifers, 4 to 12 months of age.

Procedures—Calves persistently infected with noncytopathic type 1 BVDV were treated with recombinant human interferon alfa-2a every other day for 12 weeks. Viral loads were measured during the treatment period and compared with pre- and post-treatment values. Complete physical examinations were performed weekly, and calves were observed daily for signs of systemic illness. Complete blood counts and serum biochemical analyses were performed before, during, and after the treatment period. Because calves developed anemia during the treatment period, bone marrow biopsy specimens were collected. Antirecombinant human interferon alfa-2a antibody concentrations in serum samples obtained before, during, and after the treatment period were measured by use of an ELISA.

Results—Recombinant human interferon alfa-2a had no antiviral activity against noncytopathic type 1 BVDV in persistently infected calves. All calves developed microcytic anemia during the treatment period that persisted for up to 13 weeks after cessation of treatment. Anti-interferon antibodies were detected during the treatment period and persisted for at least 2 weeks after cessation of treatment.

Conclusions and Clinical Relevance—Because of lack of in vivo antiviral activity against BVDV, recombinant human interferon alfa-2a has little promise as a therapeutic agent for the treatment of BVDV infection, at least in persistently infected cattle. Furthermore, treatment was associated with adverse immunologic and hematologic effects. (Am J Vet Res 2004;65:865–870)

Abstract

Objective—To evaluate antiviral activity and toxicity of recombinant human interferon alfa-2a in calves persistently infected with noncytopathic type 1 bovine viral diarrhea virus (BVDV).

Animals—5 Holstein heifers, 4 to 12 months of age.

Procedures—Calves persistently infected with noncytopathic type 1 BVDV were treated with recombinant human interferon alfa-2a every other day for 12 weeks. Viral loads were measured during the treatment period and compared with pre- and post-treatment values. Complete physical examinations were performed weekly, and calves were observed daily for signs of systemic illness. Complete blood counts and serum biochemical analyses were performed before, during, and after the treatment period. Because calves developed anemia during the treatment period, bone marrow biopsy specimens were collected. Antirecombinant human interferon alfa-2a antibody concentrations in serum samples obtained before, during, and after the treatment period were measured by use of an ELISA.

Results—Recombinant human interferon alfa-2a had no antiviral activity against noncytopathic type 1 BVDV in persistently infected calves. All calves developed microcytic anemia during the treatment period that persisted for up to 13 weeks after cessation of treatment. Anti-interferon antibodies were detected during the treatment period and persisted for at least 2 weeks after cessation of treatment.

Conclusions and Clinical Relevance—Because of lack of in vivo antiviral activity against BVDV, recombinant human interferon alfa-2a has little promise as a therapeutic agent for the treatment of BVDV infection, at least in persistently infected cattle. Furthermore, treatment was associated with adverse immunologic and hematologic effects. (Am J Vet Res 2004;65:865–870)