Anti-Viral Effect of Interferon-.ALPHA. on Bovine Viral Diarrhea Virus.

Abstract

ABSTRACT. To get basic information to control persistent virus infection among domestic animals by cytokines, the antiviral activity of four natural human cytokines against bovine viral diarrhea virus (BVDV) was evaluated. Normal bovine peripheral blood mononuclear leukocytes (PBML) and fetal bovine muscular cells (FBMC) were treated with varying doses of human interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α and TNF-β. The antiviral activity in treated cells was measured by the titration of virus infectivity in comparison with non-treated controls. IFN-α significantly suppressed virus growth in both PBML and FBMC. The growth of two cytopathogenic and two noncytopathogenic strains was suppressed in the presence of more than 10 3 u/ml of IFN-α. Addition of either TNF-α or TNF-β to IFN-α did not potentiate the suppressive effect. IFN-α also suppressed the replication of BVDV in PBML from cattle persistently infected with BVDV. -KEY WORDS: bovine viral diarrhea virus, cytokine, interferon, persistent infection, pestivirus.

Inhibition of Beta Interferon Transcription by Noncytopathogenic Bovine Viral Diarrhea Virus Is through an Interferon Regulatory Factor 3-Dependent Mechanism

“…We know that viruses can compromise the elaboration of IFN action: over recent years several examples of viruses that inhibit IFN signaling have been described (16). It is known that both cp and ncp BVDV are sensitive to IFN (5,35), and it is consistent with these observations that the titration of bovine IFN on ncp BVDV-infected cultures is identical to that observed in control cultures. These results indicate that ncp BVDV cannot compromise IFN signaling and extend recently published results of studies using an antiviral assay (34).…”

“…In contrast to the sensitivity of BVDV to IFN, it has been reported that TNF-␣ has no antiviral effect on cp or ncp BVDV in culture (5,35), which might suggest that TNF-␣ signaling is compromised in BVDV-infected cells. TNF-␣ signals through a series of receptors and kinases that result in the phosphorylation and proteasome degradation of the inhibitor of NF-B, IB, resulting in NF-B transport to the nucleus of the cell (31).…”

“…It has been reported that the antiviral effects of TNF-␣ are inhibited in ncp BVDVinfected cultures (5,35). To extend the observations above on NF-B induction by viruses, TNF-␣ induction of NF-B in BVDV-infected CaTe cells was examined.…”

Establishment of a Subgenomic Replicon for Bovine Viral Diarrhea Virus in Huh-7 Cells and Modulation of Interferon-Regulated Factor 3-Mediated Antiviral Response

“…Current treatment for HCV infection is (pegylated) IFN-␣ either alone or in combination with ribavirin (23). The HCV replicon has been shown to be sensitive to IFN-␣, -␤, and -␥ (7), and BVDV is known to be interferon sensitive (6,32). We compared the sensitivity of the Huh-7-BVDV and Huh-7-HCV replicons against IFN-␣, -␤, and -␥ (Fig.…”

“…BVDV has long been known to block the activity of endogenous interferon (10), but exogenously added interferons have been shown to inhibit the replication of vesicular stomatitis virus even when the cells have been coinfected with ncpBVDV (31). Human interferons, not surprisingly, have demonstrated poor activity against BVDV in bovine cells (32). We examined the effect of various human interferons on BVDV and HCV RNA replication in the same human cellular background and found that both replicons had similar susceptibilities to the interferons.…”