Novel expression and regulation of TIMP-1 in Epstein Barr virus-infected cells and its impact on cell survival

Sue Jane Lin, Shao Wen Wu, Ya Ching Chou, Jiun Han Lin, Ya Chi Huang, Mei Ru Chen, Nianhan Ma, Ching Hwa Tsai

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish
Pages (from-to)24-33
Number of pages10
JournalVirology
Volume481
DOIs
StatePublished - 1 Jul 2015

Keywords

  • Apoptosis
  • EBV
  • LCL
  • TIMP-1
  • Zta

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