» Articles » PMID: 16086371

Stable Expression of EBERs in Immortalized Nasopharyngeal Epithelial Cells Confers Resistance to Apoptotic Stress

Overview
Journal Mol Carcinog
Date 2005 Aug 9
PMID 16086371
Citations 22
Authors
Affiliations
Soon will be listed here.
Abstract

Epstein-Barr virus (EBV) infection is closely associated with the development of nasopharyngeal carcinoma (NPC). The EBV-encoded RNAs (EBERs) are the most abundant EBV transcripts (about 10(7) copies per cell) in EBV infected cells. However, the cellular function of EBER expression, particularly in nasopharyngeal epithelial cells, remains poorly understood. EBERs acquire secondary structures analogous to double-stranded RNA (dsRNA) and may bind to the double-stranded RNA-dependent protein kinase (PKR) and interfere with its function. Activation of PKR involves autophosphorylation resulting in protein synthesis inhibition and cellular apoptosis. Induction of cellular apoptosis by activation of PKR may be an antiviral response adopted by virally infected cells. We have examined the functional properties of EBER expression in an immortalized nasopharyngeal epithelial cell line (NP69). Expression of EBERs was achieved by transfecting the NP69 cells with an EBER-expressing plasmid, pESK10. The EBER-expressing NP69 cells attained a higher growth rate compared to cells transfected with control plasmid (pcDNA3). However, the EBER-expressing NP69 cells did not form colonies in soft agar and were non-tumorigenic in nude mice. To investigate if EBERs may protect the nasopharyngeal epithelial cells from apoptotic insults, we treated the EBER-expressing NP69 cells with a dsRNA analogue, poly(I).poly(C) (pIC), to activate PKR in cells and examined for their responses. Lower level of PKR phosphorylation and elevation of Bcl-2 were observed in EBER-expressing NP69 cells. In addition, other apoptotic markers including the cleaved forms of caspase-3 and poly(ADP)ribose polymerase (PARP) were found to be lower in EBER-expressing NP69 cells after treatment with pIC. Lower phosphorylation levels of p38 MAPK (mitogen-activated protein kinase) and c-jun were also observed in EBER-expressing NP cells. Our results suggest that EBER expression may confer an apoptotic-resistant phenotype in immortalized nasopharyngeal epithelial cells.

Citing Articles

Molecular diagnosis of nasopharyngeal carcinoma: Past and future.

Hsu C, Chang Y, Li H Biomed J. 2024; 48(1):100748.

PMID: 38796105 PMC: 11772973. DOI: 10.1016/j.bj.2024.100748.


Regulation mechanism of EBV-encoded EBER1 and LMP2A on YAP1 and the impact of YAP1 on the EBV infection status in EBV-associated gastric carcinoma.

Sun Y, Shi D, Sun J, Zhang Y, Liu W, Luo B Virus Res. 2024; 343:199352.

PMID: 38462175 PMC: 10982081. DOI: 10.1016/j.virusres.2024.199352.


Epstein-Barr virus infection: the micro and macro worlds.

Huang W, Bai L, Tang H Virol J. 2023; 20(1):220.

PMID: 37784180 PMC: 10546641. DOI: 10.1186/s12985-023-02187-9.


Virus-Mediated Inhibition of Apoptosis in the Context of EBV-Associated Diseases: Molecular Mechanisms and Therapeutic Perspectives.

Wyzewski Z, Mielcarska M, Gregorczyk-Zboroch K, Myszka A Int J Mol Sci. 2022; 23(13).

PMID: 35806271 PMC: 9266970. DOI: 10.3390/ijms23137265.


Anti-viral and pro-inflammatory functions of Toll-like receptors during gamma-herpesvirus infections.

Gaglia M Virol J. 2021; 18(1):218.

PMID: 34749760 PMC: 8576898. DOI: 10.1186/s12985-021-01678-x.