Page 30 - H. Cell signaling

[H. Cell signaling-24]

HSV- 1 ICP27 represses NFAT activity through regulating

calmodulin/calcineurin signaling pathway

Mi-jee Kim¹, Inho Kang¹, Jeong Keun Ahn¹

¹Department of Microbiology & Molecular Biology, College of Bioscience and Biotechnology, Chungnam National

University, Daejeon 305-764, Korea

Herpes simplex virus type 1 (HSV-1) is a human pathogenic virus which has neurotropism and latency which is
associated with viral immune escape. Among HSV-1 immediate early proteins, ICP27 is a multifunctional regulatory

protein which is essential for viral replication and viral gene expression. Nuclear factor of activated T cells (NFAT) is

a transcription factor expressed in a variety of immune cells and regulates the gene expression associated with the
immune response. A previous report showed that HSV-1 infection inhibits NFAT activity and blocks NFAT nuclear
translocation.

In this study, we report that HSV-1 ICP27 interacts with calmodulin (CaM) and inhibits NFAT signaling pathway
through regulating calcineurin. We confirmed that ICP27 physically binds to calmodulin directly. HSV-1 ICP27

interferes the association between CaM and calcineurin which is a CaM dependent ser/thr protein phosphatase.
ICP27 also suppresses the phosphatase activity of calcineurin and enhances the phosphorylation level of NFAT to

elevate NFAT responsible gene expression. These results suggest that HSV-1 ICP27 represses NFAT transcriptional
activity by regulating CaM for the viral escape from immune surveillance.