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

• Published in: Virology (New York, N.Y.) Vol. 481; pp. 24 - 33
• Main Authors: Lin, Sue-Jane, Wu, Shao-Wen, Chou, Ya-Ching, Lin, Jiun-Han, Huang, Ya-Chi, Chen, Mei-Ru, Ma, Nianhan, Tsai, Ching-Hwa
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2015
• Subjects: Apoptosis; B-Lymphocytes - metabolism; B-Lymphocytes - virology; Cell Survival; EBV; Epstein-Barr Virus Infections - genetics; Epstein-Barr Virus Infections - metabolism; Epstein-Barr Virus Infections - physiopathology; Herpesvirus 4, Human - genetics; Herpesvirus 4, Human - physiology; Humans; Infectious Disease; LCL; Promoter Regions, Genetic; Protein Binding; TIMP-1; Tissue Inhibitor of Metalloproteinase-1 - genetics; Tissue Inhibitor of Metalloproteinase-1 - metabolism; Trans-Activators - genetics; Trans-Activators - metabolism; Transcription Factor AP-1 - genetics; Transcription Factor AP-1 - metabolism; Zta; NPC; nasopharyngeal carcinoma; TIMP-1; Burkitt׳s lymphoma; post-transplant lymphoproliferative disorder; Zta; MMPs; BL; Hodgkin׳s disease; lymphoblastoid cell lines; LCL; Tissue inhibitors of metalloproteinases; EBV; TIMPs; PTLD; HD; LCLs; matrix metalloproteinases; Epstein–Barr virus; Apoptosis
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2015.02.015

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.