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


METHODS
5 Holstein heifers, 4 to 12 months of age.


METHODS
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
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.
Peek
Simon F
SF
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA.
Bonds
Michael D
MD
Schaele
Patrick
P
Weber
Sarah
S
Friedrichs
Kristin
K
Schultz
Ronald D
RD
D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology*; D000998:Antiviral Agents / Q000627:therapeutic use* / Q000633:toxicity; D001774:Blood Chemical Analysis / Q000662:veterinary; D001912:Bovine Virus Diarrhea-Mucosal Disease / Q000188:drug therapy*; D002417:Cattle; D002418:Cattle Diseases / Q000188:drug therapy*; D030241:Diarrhea Virus 1, Bovine Viral / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000276:immunology / Q000627:therapeutic use* / Q000633:toxicity; D011994:Recombinant Proteins; D019562:Viral Load / Q000662:veterinary
D000906:Antibodies; D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins