The phosphorylation profile of protein kinase A substrates is modulated during Varicella-zoster virus infection

Abstract

The cAMP-dependent protein kinase A (PKA) is a key enzyme for many cellular mechanisms. In this study, we investigated the importance of this kinase for the replication of the alphaherpesvirus Varicella-zoster virus (VZV). We report that the expression of the catalytic subunit of PKA was strongly increased at the beginning of the viral cycle. The presence of a peptide inhibitor of PKA had no consequence on viral replication in a melanoma cell line whereas in fibroblasts, it resulted in a drastic decrease of replication. An overall analysis of PKA substrates phosphorylation patterns during VZV replication showed that the phosphorylation of PKA substrates was modulated. These results were completed by investigating the accumulation and phosphorylation patterns of the PKA target cAMP response element binding protein (CREB). This transcription factor remained available throughout the VZV replication, but its phosphorylation decreased in the early phase of infection before it rose later on. These results indicate that the PKA signalling plays a cell-type dependent role for VZV replication and that the infection resulted in a regulated CREB-dependent gene expression.