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. 1997 Sep;71(9):6560–6567. doi: 10.1128/jvi.71.9.6560-6567.1997

The Epstein-Barr virus-induced Ca2+/calmodulin-dependent kinase type IV/Gr promotes a Ca(2+)-dependent switch from latency to viral replication.

T Chatila 1, N Ho 1, P Liu 1, S Liu 1, G Mosialos 1, E Kieff 1, S H Speck 1
PMCID: PMC191933  PMID: 9261377

Abstract

The switch from latency to viral replication in Epstein-Barr virus (EBV)-transformed human B cells is mediated by Zta, the protein product of immediate-early EBV gene BZLF1. BZLF1 transcription is normally suppressed in EBV-transformed B cells but can be induced in some cell lines upon ligation of surface immunoglobulin by mechanisms that include the activation of Ca(2+)-dependent signaling pathways. The multifunctional Ca2+/calmodulin-dependent kinase type IV/Gr (CaMKIV/Gr) is normally absent in primary human B cells, but its expression is induced by the EBV oncoprotein LMP1 in the course of B-cell growth transformation by EBV. In this study, we demonstrate that activated CaMKIV/Gr induces transcription from the BZLF1 promoter and upregulates the expression of Zta in permissive cells. Transcriptional activation of the BZLF1 promoter by CaMKIV/Gr is dependent on the CREB/AP1 binding element ZII and is greatly augmented by the Ca2+/calmodulin-dependent phosphatase calcineurin. These results outline a virus-regulated mechanism involving CaMKIV/Gr which promotes transition from latency to productive viral replication in response to Ca(2+)-mobilizing extracellular signals.

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Selected References

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