The biology of EBV infection in human epithelial cells

Tsao, Sai Wah; Tsang, Chi Man; Pang, Polly; Zhang, Guitao; Chen, Honglin; Lo, Kwok Wai

doi:10.1016/j.semcancer.2012.02.004

Cited by 99 publications

(93 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It has been reported that EBV is associated with 10% of gastric carcinomas and that in most cases positive EBV is diagnosed in poorly differentiated or moderately differentiated grades [23,24]. The progress of any malignancy associated with EBV requires the establishment of complex cell interactions in epithelial cells and specific viral gene expression.…”

Section: Discussionmentioning

confidence: 99%

Original paper Epstein-Barr virus DNA in colorectal carcinoma in Iranian patients

Tafvizi¹,

Fard²,

Assareh³

2015

pjp

View full text Add to dashboard Cite

Colorectal cancer is an often fatal cancer with a rapidly increasing incidence. Current mortality is estimated to be approximately 600,000 per year, and both environmental and genetic factors are involved in its etiology. Viral and bacterial factors have a proven role in the incidence of approximately 20% of cancers. In the present study, the Epstein-Barr virus (EBV) was detected in 50 colorectal adenocarcinomas, 12 colon adenomas, and 38 control tissue samples using polymerase chain reaction (PCR). Epstein-Barr virus DNA was identified in 19 of the adenocarcinoma tissues, 1 adenoma tissue and 24 control specimens. In total, 15.8% (3/18) of the colorectal samples in the well-differentiated grade, 79% (15/30) in the moderately differentiated, and 5.2% (1/2) in the poorly differentiated grade tested positive for viral infection. Epstein-Barr virus was more prevalent in the moderately differentiated grade. Statistical analysis did not suggest a significant association between EBV and the incidence of colorectal cancer. However, it appears that the virus stimulates progression of the malignancy.

show abstract

Section: Discussionmentioning

confidence: 99%

Original paper Epstein-Barr virus DNA in colorectal carcinoma in Iranian patients

Tafvizi¹,

Fard²,

Assareh³

2015

pjp

View full text Add to dashboard Cite

show abstract

“…More than 90% of the adult population is latently infected, and a subset can develop EBV-associated malignancies, including nasopharyngeal carcinoma (NPC), gastric cancer, Burkitt lymphoma, Hodgkin lymphoma, and lymphomas in the immunocompromised, including AIDS-associated lymphoma and posttransplant lymphoproliferative disease (2,3). Epithelial cell infection in vitro frequently results in productive replication, and latently infected oral epithelial cells are rare in persistently infected healthy individuals (4,5). However, epithelial tumors such as NPC consistently express a type II latency program, which includes latent membrane protein 1 (LMP1), LMP2A, and LMP2B (1,5).…”

Section: Importancementioning

confidence: 99%

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

Wasil

Wei

Chang

et al. 2015

J Virol

View full text Add to dashboard Cite

Nasopharyngeal carcinoma (NPC) is closely associated with latent Epstein-Barr virus (EBV) infection. Although EBV infection of preneoplastic epithelial cells is not immortalizing, EBVcan modulate oncogenic and cell death mechanisms. The viral latent membrane proteins 1 (LMP1) and LMP2A are consistently expressed in NPC and can cooperate in bitransgenic mice expressed from the keratin-14 promoter to enhance carcinoma development in an epithelial chemical carcinogenesis model. In this study, LMP1 and LMP2A were coexpressed in the EBV-negative NPC cell line HK1 and examined for combined effects in response to genotoxic treatments. In response to DNA damage activation, LMP1 and LMP2A coexpression reduced ␥H2AX (S139) phosphorylation and caspase cleavage induced by a lower dose (5 M) of the topoisomerase II inhibitor etoposide. Regulation of ␥H2AX occurred before the onset of caspase activation without modulation of other DNA damage signaling mediators, including ATM, Chk1, or Chk2, and additionally was suppressed by inducers of DNA single-strand breaks (SSBs) and replication stress. Despite reduced DNA damage repair signaling, LMP1-2A coexpressing cells recovered from cytotoxic doses of etoposide; however, LMP1 expression was sufficient for this effect. LMP1 and LMP2A coexpression did not enhance cell growth, with a moderate increase of cell motility to fibronectin. This study supports that LMP1 and LMP2A jointly regulate DNA repair signaling and cell death activation with no further enhancement in the growth properties of neoplastic cells. E pstein-Barr virus (EBV) is a human gammaherpesvirus that establishes lifelong latency in memory B cells, with sporadic reactivation and transmission from oral epithelia (1). More than 90% of the adult population is latently infected, and a subset can develop EBV-associated malignancies, including nasopharyngeal carcinoma (NPC), gastric cancer, Burkitt lymphoma, Hodgkin lymphoma, and lymphomas in the immunocompromised, including AIDS-associated lymphoma and posttransplant lymphoproliferative disease (2, 3). Epithelial cell infection in vitro frequently results in productive replication, and latently infected oral epithelial cells are rare in persistently infected healthy individuals (4, 5). However, epithelial tumors such as NPC consistently express a type II latency program, which includes latent membrane protein 1 (LMP1), LMP2A, and LMP2B (1, 5). Additionally, monoclonal EBV episomes are detected in NPC, suggesting that NPC tumors are the clonal outgrowth of an initially infected cell likely predisposed to oncogenic transformation from additional genetic and environmental cofactors, such as the loss of p16 and exposure to dietary nitrosamines (2, 3). In contrast to the immortalizing properties of EBV to primary B cells, the contribution of EBV infection to epithelial cell oncogenesis is less understood, as infection alone is insufficient to immortalize or induce oncogenic potential in preneoplastic cell lines from the nasopharynx (5, 6).LMP1 and LMP2A transcripts are ...

show abstract

“…The two main shortcomings are: 1. the lack of human epithelial cells, which does not allow for the complete examination of EBV life cycle stages including viral titers during entry into the human body or during shedding into the saliva (Tsao et al, 2012), and 2. the limited differentiation from naïve B cells to memory and plasma B cells, which compromises both the humoral immune responses to EBV infection and the access of the virus to lower latency programs besides latency III (Thorley-Lawson and Allday, 2008). These aspects might be better modeled in monkeys, which harbor close relatives of EBV.…”

Section: Lymphocryptoviruses In Monkeysmentioning

confidence: 99%

Animal models of Epstein Barr virus infection

Chatterjee

Leung

Münz

2014

Journal of Immunological Methods

View full text Add to dashboard Cite

Epstein Barr virus (EBV) was the first human tumor virus to be identified. Despite 50years of research on this oncogenic virus, no therapeutic or prophylactic vaccine is available against this pathogen. In part, the development of such a vaccine is hampered by the lack of in vivo models for EBV infection and immune control. However, with the advent of mice with reconstituted human immune system components (HIS mice), certain aspects of EBV associated diseases and immune responses can be modeled in vivo. In this review, we will discuss the insights that can be gained from these experiments, and how immune system components can be manipulated to interrogate their function during EBV infection. Finally, we will compare EBV immunobiology in HIS mice to infection by EBV-related viruses in monkeys, and we will outline the strengths and weaknesses of these two in vivo models of EBV infection. Both of these models show great promise as a platform for preclinical EBV vaccine testing. AbstractEpstein Barr virus (EBV) was the first human tumor virus to be identified. Despite 50 years of research on this oncogenic virus, no therapeutic or prophylactic vaccine is available against this pathogen. In part, the development of such a vaccine is hampered by the lack of in vivo models for EBV infection and immune control. However, with the advent of mice with reconstituted human immune system components (HIS mice), certain aspects of EBV associated diseases and immune responses can be modeled in vivo. In this review, we will discuss the insights that can be gained from these experiments, and how immune system components can be manipulated to interrogate their function during EBV infection. Finally, we will compare EBV immunobiology in HIS mice to infection by EBV-related viruses in monkeys, and we will outline the strengths and weaknesses of these two in vivo models of EBV infection. Both of these models show great promise as a platform for preclinical EBV vaccine testing. Chatterjee et al. 3

show abstract

The biology of EBV infection in human epithelial cells

Cited by 99 publications

References 59 publications

Original paper Epstein-Barr virus DNA in colorectal carcinoma in Iranian patients

Original paper Epstein-Barr virus DNA in colorectal carcinoma in Iranian patients

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

Animal models of Epstein Barr virus infection

Contact Info

Product

Resources

About