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
Objective—To evaluate cytotoxicity and antiviral
activity of recombinant human interferon alfa-2a and
recombinant human interferon alfa-B/D hybrid against
cytopathic and noncytopathic bovine viral diarrhea
virus (BVDV), infectious bovine rhinotracheitis virus
(IBRV), and vesicular stomatitis virus (VSV) in vitro.
Sample population—Primary bovine testicular cells
and Mardin Darby bovine kidney cells.
Procedures—To evaluate cytotoxicity, cells were added
to serial dilutions of each interferon. To evaluate antiviral
activity of each interferon, interferons were serially diluted
1:10, and tissue culture cells were added; virus was
then added at 3 time points. Prevention of viral infection
by interferon was defined as failure to induce cytopathologic
effect for VSV, IBRV, and cytopathic BVDV and failure
to detect virus immunohistochemically for cytopathic
and noncytopathic BVDV.
Results—No evidence of cytotoxicity in either cell
line was detected after incubation with interferon alfa-
2a or interferon alfa-B/D. However, reduced growth
rates of tissue culture cells were detected for each
interferon when undiluted interferon was tested.
Comparable and profound antiviral activities against
cytopathic and noncytopathic BVDV were evident for
each interferon. Interferon alfa-2a and interferon a-B/D
had comparable antiviral activities against VSV.
Neither interferon had antiviral activity against IBRV.
Conclusions and Clinical Relevance—The safety
and marked in vitro antiviral activity against noncytopathic
BVDV, cytopathic BVDV, and VSV suggest that
interferons alfa-2a and alfa-B/D may be useful for
treatment of natural disease after infection with these
viruses. (Am J Vet Res 2004;65:871–874)