Epstein-Barr virus lytic reactivation regulation and its pathogenic role in carcinogenesis

Li, Hongde; Liu, Sufang; Hu, Jianmin; Luo, Xiangjian; Li, Namei; Bode, Ann M.; Cao, Yang

doi:10.7150/ijbs.16564

Cited by 106 publications

(118 citation statements)

References 109 publications

(119 reference statements)

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“…LMP1 has been be detected in 90% of patients with NPC (18,19). Through its cytoplasmic C-terminus, LMP1 has been reported to trigger multiple signal transduction cascades associated with the EBV lytic cycle, including MEK/ERK, PI3-K/Akt, nuclear factor-κB and JNK signaling pathways (20,21). In addition, the LMP1 gene of several EBV strains also contains a late lytic cycle promoter, EDL1A, which drives the expression of an amino-terminally truncated form of LMP1, lytic LMP1 (lyLMP1).…”

Section: Discussionmentioning

confidence: 99%

“…Through its cytoplasmic C-terminal, LMP1 may trigger multiple signal transduction cascades, including the MAPK kinase (MEK)/extracellular signal-regulated kinase (ERK), PI3-K/Akt, c-Jun N-terminal kinase (JNK) and signal transducer and activator of transcription 3 signaling pathways, to alter cell growth and survival (20,21). Furthermore, LMP1 is established as a critical viral protein required for the EBV life cycle (13,(22)(23)(24)(25).…”

Section: Introductionmentioning

confidence: 99%

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(-)-Epigallocatechin‑3‑gallate inhibition of Epstein‑Barr virus spontaneous lytic infection involves downregulation of latent membrane protein 1

Liu

Tang

et al. 2017

Exp Ther Med

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Abstract. The Epstein-Barr virus (EBV) lytic cycle contributes to the development of EBV-associated diseases. EBV-encoded latent membrane protein 1 (LMP1) is key to EBV lytic replication, and our previous work indicated that epigallocatechin-3-gallate (EGCG) inhibited constitutive EBV lytic infection through the suppression of LMP1-activated phosphoinositide 3-kinase/Akt and mitogen-activated protein kinase kinase/extracellular signal-related protein kinase 1/2 signaling. The present study demonstrated that LMP1 in CNE-LMP1 constructed cells significantly induced the expression of the EBV lytic proteins BZLF1 (P<0.001) and BMRF1 (P<0.05) compared with CNE1 cells. Following treatment with a specific DNAzyme that targets LMP1, significantly reduced protein expression levels of BZLF1 and BMRF1 in EBV-associated epithelial carcinoma CNE1-LMP1 cells (P<0.001 and P<0.01, respectively) and lymphoma B95.8 cells (both P<0.01) were observed. Furthermore, EGCG significantly inhibited the mRNA and protein expression levels of LMP1 (P<0.05) in an apparent dose-dependent manner in CNE1-LMP1 and B95.8 cells. Thus, the present findings indicated that the molecular mechanism underlying EGCG inhibition of EBV lytic infection involves downregulation of LMP1. IntroductionEpstein-Barr virus (EBV) is a human herpes virus that infects over 90% of the human population worldwide (1). EBV is suggested to be an environmental factor associated with the development of several human malignancies, including nasopharyngeal carcinoma (NPC), Burkitt's lymphoma, Hodgkin's disease (HD), gastric cancer, natural killer/T-cell lymphoma, acquired immune deficiency syndrome-and transplantation-associated lymphoma (2,3), breast carcinoma, and hepatocellular carcinoma (4,5). EBV, as all other herpes viruses, may establish a latent or lytic infection in host cells (6). Notably, studies suggest that EBV reactivation into a lytic cycle may contribute to the pathogenesis of malignancies (7,8). EBV lytic infection in vivo has been identified by elevated antibody titers against EBV lytic antigens and by increased viral DNA load in the serum/plasma, and these observations correspond with advanced cancer stages, poor prognosis or tumor recurrence following therapy (9,10). Additionally, serological studies have indicated that EBV lytic infection may occur months or years prior to a clinical diagnosis of NPC, HD or Burkitt's lymphoma, which suggests EBV lytic infection may be a risk factor for cancer development (11-13).Green tea contains (-)-epigallocatechin-3-gallate (EGCG), which is reported to have antioxidant, antibacterial and antitumor effects (14,15). EGCG has been indicated to modulate multiple signaling pathways, including the phosphoinositide 3-kinase (PI3-K)/Akt and mitogen-activated protein kinase (MAPK) signaling pathways, which may enable it to exert its cancer chemopreventive and therapeutic effects (16,17).EBV encoded latent membrane protein 1 (LMP1), which is considered to have oncogenic properties, has been identified in 90% of patients with NPC...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

(-)-Epigallocatechin‑3‑gallate inhibition of Epstein‑Barr virus spontaneous lytic infection involves downregulation of latent membrane protein 1

Liu

Tang

et al. 2017

Exp Ther Med

Self Cite

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“…attachment anxiety,(Fagundes et al, 2014) psychosocial stress,(Glaser et al, 1985; Glaser et al, 1994) and exposure to adverse life events(McDade et al, 2000)), is also be associated with reactivation of latent herpes viruses, including the Epstein-Barr virus (EBV) – a latent virus linked to certain autoimmune disorders,(Niller et al, 2008) cancer(Li et al, 2016) and athersclerosis. (Espinola-Klein et al, 2002) In the U.S., primary infection with EBV is nearly ubiquitous by young adulthood, and although the virus is most well- known for causing mononucleosis during adolescence, the majority of the population experience primary infection earlier in childhood with few to no symptoms.…”

Section: 0 Introductionmentioning

confidence: 99%

Depressive symptoms are associated with salivary shedding of Epstein-Barr virus in female adolescents: The role of sex differences

Ford

Stowe

2017

Psychoneuroendocrinology

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Background Adolescent females have a higher prevalence of depression in comparison to their male peers - a disparity that has been increasing over the past decade. Depression is of concern as it is associated with chronic disease and to immune dysregulation, which may be one mechanism linking depression to future pathology. This study examined the extent to which sex moderated the association between depressive symptoms and immune dysregulation during adolescence using Epstein-Barr virus (EBV) reactivation, a biomarker of cellular immune response, as a model. Methods A representative community sample of 259 female and 279 male adolescents aged 11 to 17 years who were EBV IgG positive were examined. Trained interviewers collected the data during two home visits, one week apart. Depressive symptoms were measured at the first visit using the 9 item short-form of the Center for Epidemiologic Studies-Depression scale. EBV biomarkers were collected via saliva at the second visit and included a qualitative measure of EBV viral capsid antigen immunoglobulin G to assess prior EBV infection and a quantitative measure of EBV DNA to assess the number of viral copies shed in the saliva. Results In multivariable logistic regression analyses, increasing depressive symptoms were significantly associated with salivary shedding of EBV DNA for adolescent females only (logit=0.66, se=0.30, p<0.05), and the interaction between sex and depressive symptoms on salivary shedding of EBV DNA was statistically significant (logit= −1.19, se=0.42, p<0.01). Sensitivity analyses were conducted in which sex was examined as a moderator in the relationship between depressive symptoms and salivary EBV DNA quantitative copies via Tobit regression; results were consistent with the presented findings. Conclusions Depressive symptoms are associated with EBV reactivation among EBV positive female adolescents, but not males. Future research is needed to examine EBV reactivation in female adolescents as a mechanism linking depression to future chronic disease and the role of sex hormones in explaining sex differences in the relationship between depressive symptoms and EBV reactivation.

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“…The higher infection rate among females is probably due to their more biological vulnerability to HSV-2 infection [9]. HSV type 1 (HSV-1) usually causes non-sexually-transmitted oral herpes infection.EBV is an oncogenic virus that is associated with a number of cancers, such as Hodgkin's lymphoma (HL), Burkett's lymphoma (BL), nasopharyngeal carcinoma (NPC), and gastric carcinoma [10,11]. EBV contributes to the initiation, development and promotion of malignancies via the introduction of growth factors and oncogenic cytokine production [12][13][14].…”

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confidence: 99%

Association between HPV, CMV, EBV and HS Viruses and Breast Cancer in Saudi Arabia

Alshammari¹

2017

JCPCR

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Viruses including Human papillomavirus (HPV), Herpes Simples (HSV), Epstein Barr Virus (EBV), and Human Cytomegalovirus (CMV) infections are believed to be associated with many cancers. It is well established that infection by highrisk HPVs (HR-HPVs) is considered as a major cause of several human carcinomas including cervical carcinoma, head and neck, colorectal and breast cancers. HSV, EBV, and CMV were also reported to have some role in the pathogenesis of human cancers. The association between these viruses and human malignancies would necessitate the introduction of vaccines which may reduce the burden of viral associated cancers. The assessment of the contribution of HR-HPVs, HSV, EBV, and HCMV in the pathogenesis of breast cancer in the Kingdom of Saudi Arabia (KSA) is essential in order to evaluate the burden of these viruses, which has not been entirely studied yet. This review, presented an overview of the present epidemiological evidences regarding the presence of these viruses in human cancers with especial stress in breast cancer and the potential impact of these viruses in KSA.PubMed was searched using search terms included: Human papillomavirus (HPV), Herpes simplex virus, Herpes simplex virus 1, (HSV-1,2), Epstein Barr Virus (EBV), Human Cytomegalovirus (CMV), Breast cancer, and Saudi Arabia. Keywords: HPVs; EBV; HS; CMV; Saudi Arabia IntroductionIn recent years, there is a greater number of cancers are directly linked to infections with several viruses. It is well established that approximately 20% of the global human cancer can be attributed to virus infections [1]. Improvement in this field of research has transpired through analysis of cell signaling and growth control pathways that may be changed by the oncogenic viruses [2].HPV is the commonest sexually transmitted infections that associated with cancers worldwide. About 96% of cases of cervical cancer were found positive for high-risk HPVs, especially types 16 and 18 [3]. HR-HPVs may have a contributory part in some breast cancers [4,5]. HR-HPVs have been identified in benign breast tissues of the same type as in breast tumors, which later developed into cancer in the same patients [6].Nevertheless, only small proportion of HPV-positive cases progress in to malignancy, showing that HPV is indispensable but not enough in carcinogenesis. A number of biological and environmental cofactors have been involved in the progress of HPV-related carcinoma that includes co-infection with other sexually transmissible viruses. Such cofactors are expected to contribute to HPV persistent infection through miscellaneous mechanisms associated with immune control, effectiveness of HPV infection, and influences on tumor initiation and evolution [7]. Therefore, HPV co-infection with other factors may also possess anti-tumor properties. Thus, this review beside HPV assessed the role of (HSV-1,2), HCMV, and EBV in breast cancer.Herpes simplex virus type 2 (HSV-2) is the commonest cause of genital ulcers in several regions around the world. HSV-2 annually...

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Epstein-Barr virus lytic reactivation regulation and its pathogenic role in carcinogenesis

Cited by 106 publications

References 109 publications

(-)-Epigallocatechin‑3‑gallate inhibition of Epstein‑Barr virus spontaneous lytic infection involves downregulation of latent membrane protein 1

(-)-Epigallocatechin‑3‑gallate inhibition of Epstein‑Barr virus spontaneous lytic infection involves downregulation of latent membrane protein 1

Depressive symptoms are associated with salivary shedding of Epstein-Barr virus in female adolescents: The role of sex differences

Association between HPV, CMV, EBV and HS Viruses and Breast Cancer in Saudi Arabia

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