Our previous studies have demonstrated that
2,3,7,8-tetrachlorodibenzo-p-dioxin (
TCDD) increases Bovine Herpesvirus 1 (BHV-1) replication through a dose-dependent increase in cytopathy and increased viral titer. Furthermore,
TCDD was able to trigger BHV-1-induced apoptosis by up-regulating the activation of
initiator caspases 8 and 9, as well as of effector
caspase 3. Since
TCDD activates
caspase 3 after 4 h of
infection, we have hypothesized an involvement of BHV-1 infected cell
protein 0 (bICP0) in this process. Such
protein, the major transcriptional regulatory
protein of BHV-1, has been shown to indirectly induce
caspase 3 activation and apoptosis. In order to elucidate the role of bICP0 in this apoptotic pathway, here we have analyzed the effects of
TCDD on bICP0 expression. Following
infection of bovine cells with BHV-1, we detected apoptotic features already at 12 h after
infection, only in
TCDD exposed groups. Furthermore, in the presence of different doses of
TCDD, we observed a time-dependent modulation and increase of bICP0 gene expression levels, as revealed by RT-PCR analysis. Western blot analysis and immunocytochemistry revealed that
TCDD induced an increase of bICP0
protein levels in a dose-dependent manner, compared to unexposed groups. Moreover, Western blot analysis of nuclear and cytosolic fractions of infected cells revealed that
TCDD anticipated the presence of bICP0
protein in the cytoplasm. In conclusion, both the increase of replication of BHV-1 and anticipation of BHV-1-induced apoptosis could be the result of a relationship between
TCDD and bICP0.