Epstein-Barr Virus Infection Alters Cellular Signal Cascades in Human Nasopharyngeal Epithelial Cells

Abstract

Epstein-Barr virus (EBV) latent infection is a critical event in nasopharyngeal carcinoma (NPC) tumorigenesis. EBV-encoded genes have been shown to be involved in immune evasion and in the regulation of various cellular signaling cascades. To elucidate the roles of EBV in NPC development, stable infection of EBV in nasopharyngeal epithelial cell lines was established. Similar to primary tumors of NPC, these infected cells exhibited a type II EBV latency expression pattern. In this study, multiple cellular signaling pathways in EBV-infected cells were investigated. We first demonstrated that in vitro EBV infection resulted in the activation of STAT3 and NFkappaB signal cascades in nasopharyngeal epithelial cells. Increased expression of their downstream targets (c-Myc, Bcl-xL, IL-6, LIF, SOCS-1, SOCS-3, VEGF, and COX-2) was also observed. Moreover, EBV latent infection induced the suppression of p38-MAPK activities, but did not activate PKR cascade. Our findings suggest that EBV latent infection is able to manipulate multiple cellular signal cascades to protect infected cells from immunologic attack and to facilitate cancer development.

Disease and Carrier Isolates of Neisseria meningitidis Cause G 1 Cell Cycle Arrest in Human Epithelial Cells

“…NP69 cells were established from primary nonmalignant nasopharyngeal epithelial cells and may represent a model of premalignant nasopharyngeal epithelial cells (34,54). The cell line was used to study Epstein-Barr virus interactions with the host cell (54,55).…”

Matrix metalloproteinase 12 is induced by heterogeneous nuclear ribonucleoprotein K and promotes migration and invasion in nasopharyngeal carcinoma

“…Furthermore, it has been reported that the response of NPC cells to EBV infection is mediated mainly by the NF-κB and STAT3 signal cascades [56]. EBV infection has been known to lead to NPC tumorigenesis.…”

Regulation of DNA Damage Signaling and Cell Death Responses by Epstein-Barr Virus Latent Membrane Protein 1 (LMP1) and LMP2A in Nasopharyngeal Carcinoma Cells

“…Pooled stable HK1 cell lines were maintained in neomycin and puromycin selection media and used for further analysis. EBV-infected HK1 (gift from George Tsao, Hong Kong University) and 293 (gift from Wolfgang Hammerschmidt, Helmholtz Center) cells were maintained in neomycin (800 g/ml) and hygromycin (100 g/ml) selection media, respectively (34,35). Infected cell lines were treated with 10 M MG132 for 8 h or 2 mM methyl-beta cyclodextrin overnight for LMP1 and LMP2A expression analyses.…”