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

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

9 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 - 01 07 2015

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Inc.

Keywords

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

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