Epstein-Barr virus: clinical and epidemiological revisits and genetic basis of oncogenesis

Epstein-Barr virus (EBV) is classified as a member in the order herpesvirales, family herpesviridae, subfamily gammaherpesvirinae and the genus lymphocytovirus. The virus is an exclusively human pathogen and thus also termed as human herpesvirus 4 (HHV4). It was the first oncogenic virus recognized and has been incriminated in the causation of tumors of both lymphatic and epithelial nature. It was reported in some previous studies that 95% of the population worldwide are serologically positive to the virus. Clinically, EBV primary infection is almost silent, persisting as a life-long asymptomatic latent infection in B cells although it may be responsible for a transient clinical syndrome called infectious mononucleosis. Following reactivation of the virus from latency due to immunocompromised status, EBV was found to be associated with several tumors. EBV linked to oncogenesis as detected in lymphoid tumors such as Burkitt's lymphoma (BL), Hodgkin's disease (HD), post-transplant lymphoproliferative disorders (PTLD) and T-cell lymphomas (e.g. Peripheral T-cell lymphomas; PTCL and Anaplastic large cell lymphomas; ALCL). It is also linked to epithelial tumors such as nasopharyngeal carcinoma (NPC), gastric carcinomas and oral hairy leukoplakia (OHL). In vitro, EBV many studies have demonstrated its ability to transform B cells into lymphoblastoid cell lines (LCLs). Despite these malignancies showing different clinical and epidemiological patterns when studied, genetic studies have suggested that these EBV- associated transformations were characterized generally by low level of virus gene expression with only the latent virus proteins (LVPs) upregulated in both tumors and LCLs. In this review, we summarize some clinical and epidemiological features of EBV- associated tumors. We also discuss how EBV latent genes may lead to oncogenesis in the different clinical malignancie

Role of serum EBV-VCA IgG detection in assessing gastric cancer risk and prognosis in Northern Chinese population

Abstract The study aimed to investigate the role of serum EBV‐VCA IgG in assessing gastric cancer (GC) risk and prognosis. A total of 1790 Northern Chinese participants with pathologically confirmed disease underwent EBV‐VCA IgG serologic testing using enzyme‐linked immunosorbent assay (ELISA), including 821 controls, 410 atrophic gastritis (AG) patients, and 559 GC patients. We found that positive EBV‐VCA IgG was significantly associated with GC and its precursor, conferring a 1.55‐ and 1.36‐fold increased risk of GC and AG, respectively (P = 0.001, 95% CI = 1.21‐1.99; P = 0.011, 95% CI = 1.07‐1.72, respectively). The risk effects were more remarkable in younger, female, and Helicobacter pylori‐negative individuals than in older, male, and H. pylori‐positive individuals. EBV‐VCA IgG‐positive subjects had a lower PGI/II ratio than EBV‐VCA IgG‐negative subjects (median 8.0 vs 8.8, P = 0.001), especially those in the H. pylori‐positive (median 6.1 vs 6.8, P = 0.027) and GC subgroups (median 6.4 vs 7.9, P = 0.020). In the intestinal GC subgroup, the survival of EBV‐VCA IgG‐positive patients was worse than that of EBV‐VCA IgG‐negative patients (P = 0.041, HR = 2.45, 95% CI = 1.04‐5.78). Our study suggests that EBV‐VCA IgG seropositivity has potential in predicting the risk of GC and its precursor as well as the prognosis of histologically classified GC

Epstein-Barr Virus Infection Is Common in Inflamed Gastrointestinal Mucosa

BACKGROUND AND AIMS: Epstein-Barr virus (EBV) is present in the malignant epithelial cells of 10% of all gastric adenocarcinomas, however localization of the virus in normal gastrointestinal mucosa is largely unexplored. In the current study, we measured EBV DNA and localized viral gene products in gastritis specimens (n=89), normal gastric and colonic mucosa (n=14), Crohn’s disease (n=9), and ulcerative colitis (n=11) tissues. METHODS: A battery of sensitive and specific quantitative polymerase chain reactions targeted six disparate regions of the EBV genome: BamH1W, EBNA1, LMP1, LMP2, BZLF1, and EBER1. EBV infection was localized by EBV-encoded RNA (EBER) in situ hybridization and by immunohistochemical stains for viral latent proteins LMP1 and LMP2 and for viral lytic proteins BMRF1 and BZLF1. B lymphocytes were identified using CD20 immunostains. RESULTS: EBV DNA was essentially undetectable in normal gastric mucosa but was present in 46% of gastritis lesions, 44% of normal colonic mucosa, 55% of Crohn’s disease, and 64% of ulcerative colitis samples. Levels of EBV DNA exceeded what would be expected based on the numbers of B lymphocytes in inflamed tissues, suggesting that EBV is preferentially localized to inflammatory gastrointestinal lesions. Histochemical staining revealed EBER expression in lymphoid cells of some PCR-positive lesions. The viral lytic viral proteins, BMRF1 and BZLF1, were expressed in lymphoid cells of two ulcerative colitis tissues, both of which had relatively high viral loads by quantitative PCR. CONCLUSION: EBV-infected lymphocytes are frequently present in inflamed gastric and colonic mucosa. Active viral replication in some lesions raises the possibility of virus-related perpetuation of gastrointestinal inflammation