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Novel expression and regulation of TIMP-1 in Epstein Barr virus-infected cells and its impact on cell survival
Sue-Jane Lin1, Shao-Wen Wu2, Ya-Ching Chou2
1Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; Graduate institute of Medical Biotechnology, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
Abstract:
Epstein Barr virus (EBV) uses various strategies to manipulate host cytokine production in favor of the survival of infected B-cells. Microarray and cytokine protein array assays revealed that tissue inhibitor of metalloproteinase-1 (TIMP-1) was significantly up-regulated in EBV-infected primary B cells and maintained in abundance in EBV-immortalized lymphoblastoid cell lines (LCLs). TIMP-1 plays critical roles in extracellular matrix homeostasis and regulates signaling pathways. In this study, we demonstrated that the EBV-encoded immediate early lytic protein, Zta, upregulates mainly TIMP-1 expression by binding to the AP-1 site within the TIMP-1 promoter. Moreover, knockdown of TIMP-1 expression promoted cisplastin and cold shock-induced death of LCLs. This study provides a mechanistic link between EBV-induced TIMP-1 expression and its impact on LCL survival.
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