Alpha/beta and gamma interferons are induced by infection with noncytopathic bovine viral diarrhea virus in vivo

Abstract

In contrast to the results of previous in vitro studies, experimental infection of calves with noncytopathic bovine viral diarrhea virus (ncpBVDV) was found to induce strong alpha/beta and gamma interferon responses in gnotobiotic animals. These responses were associated with depressed levels of transforming growth factor beta (TGF-beta) in serum. The results of this study indicate that the immunosuppression caused by ncpBVDV is not associated with low interferon responses or elevated levels of TGF-beta.

FIG. 1.

Mean viral titers in the sera of six gnotobiotic calves challenged intranasally with 5 × 10⁶ PFU of ncpBVDV 11249. The bars show the mean titers (PFU per milliliter) ± standard errors of the means (SEM).

FIG. 2.

Cell proliferation (A) and IFN-γ production (B) in response to PPD-B in blood from gnotobiotic calves. Calves were infected with either BVDV and BCG (i and ii) or BCG alone (iii). BVDV challenge was performed on day 0; BCG challenge had been performed 28 days previously. Cell proliferation in each sample was analyzed in triplicate, and mean values ± standard deviations (error bars) are shown. IFN-γ production in each sample was analyzed in duplicate, and mean values are shown.

FIG. 3.

Mx expression in bovine monocytes infected either with mock antigen or with ncpBVDV 11249 or stimulated with poly(I-C) (1 μg/ml). Mx protein was detected only in monocytes treated with poly(I-C).

FIG. 4.

Kinetics of IFN-α/β production in the sera of calves after intranasal challenge infection with 5 × 10⁶ PFU of ncpBVDV isolate 11249 (⧫). Individual samples were analyzed in duplicate, and the mean values were determined. Titers are expressed as the means of values for six animals ± SEM. Titers for the mock-infected animal are shown separately (▪).

FIG. 5.

Kinetics of IFN-γ production (nanograms per milliliter) in the sera of gnotobiotic calves after intranasal challenge with 5 × 10⁶ PFU of ncpBVDV isolate 11249 (⧫). Individual samples were analyzed in duplicate, and the mean values were determined. Titers are expressed as the means of values for six animals ± SEM. Titers for the mock-infected animal are shown separately (▪).

FIG. 6.

Profiles of TGF-β in sera from gnotobiotic calves challenged intranasally with 5 × 10⁶ PFU of ncpBVDV isolate 11249. Sera were added to the TGF-β1 assay either directly (A) or after activation by acidification (B). Individual samples were analyzed in duplicate, and the mean values were determined. Open bars show the mean values for six gnotobiotic calves ± SEM. Solid bars show the values for the mock-infected animal.