Radiation-induced Epstein–Barr virus reactivation in gastric cancer cells with latent EBV infection

Abstract

Epstein–Barr virus, a ubiquitous human herpes virus with oncogenic activity, can be found in 6%–16% of gastric carcinomas worldwide. In Epstein–Barr virus–associated gastric carcinoma, only a few latent genes of the virus are expressed. Ionizing irradiation was shown to induce lytic Epstein–Barr virus infection in lymphoblastoid cell lines with latent Epstein–Barr virus infection. In this study, we examined the effect of ionizing radiation on the Epstein–Barr virus reactivation in a gastric epithelial cancer cell line (SNU-719, an Epstein–Barr virus–associated gastric carcinoma cell line). Irradiation with X-ray (dose = 5 and 10 Gy; dose rate = 0.5398 Gy/min) killed approximately 25% and 50% of cultured SNU-719 cells, respectively, in 48 h. Ionizing radiation increased the messenger RNA expression of immediate early Epstein–Barr virus lytic genes (BZLF1 and BRLF1), determined by real-time reverse transcription polymerase chain reaction, in a dose-dependent manner at 48 h and, to a slightly lesser extent, at 72 h after irradiation. Similar findings were observed for other Epstein–Barr virus lytic genes (BMRF1, BLLF1, and BcLF1). After radiation, the expression of transforming growth factor beta 1 messenger RNA increased and reached a peak in 12–24 h, and the high-level expression of the Epstein–Barr virus immediate early genes can convert latent Epstein–Barr virus infection into the lytic form and result in the release of infectious Epstein–Barr virus. To conclude, Ionizing radiation activates lytic Epstein–Barr virus gene expression in the SNU-719 cell line mainly through nuclear factor kappaB activation. We made a brief review of literature to explore underlying mechanism involved in transforming growth factor beta–induced Epstein–Barr virus reactivation. A possible involvement of nuclear factor kappaB was hypothesized.

Infection Load and Prevalence of Novel Viruses Identified from the Bank Vole Do Not Associate with Exposure to Environmental Radioactivity

“…The effects of environmental radiation on host-viral dynamics in natural systems are unknown. While high doses (in excess of several kilograys, kGy) of ionizing radiation inactivate viruses [19,20], exposure to lower doses (2.5-25 Gy) can activate replication in some viruses, such as cytomegalovirus [21], endogenous retroviruses [22], human immunodeficiency virus [23], hepatitis B virus [24,25], Epstein-Barr virus [26,27], reovirus [28], herpes simplex virus [29], parvoviruses [30,31], and poliovirus [32]. Virus activation by irradiation may be facilitated by radiation-mediated immunosuppression that makes the host more susceptible to virus infection and replication [33][34][35], or by radiation-induced activation of the DNA repair proteins that some viruses utilize in their replication [36,37].…”

Apoptosis- and survival-related gene mRNA profile in peripheral blood leukocytes in children with acute EBV infectious mononucleosis

“…Так, в ВЭБ-трансформированных B-клетках при учас тии белка ВЭБ BARF1 повышалась экспрессия RELA, усиливающая пролиферацию инфицированных лимфоцитов [10,11]. В то же время ВЭБ-опосредованное повышение уровней мРНК RELB наблюдалось при реактивации ВЭБ в клеточных линиях рака желудка [37]. В период реконвалесценции уровни мРНК ряда инициаторных (TRAF2-NM_021138, NIK/ MAP3K14-Σ) и эффекторных (p50/NFKB1-Σ, RELB-NM_006509) элементов NF-κB-зависимого сигналинга оставались повышенными, что может быть обусловлено, с одной стороны, «остаточной» вирусиндуцированной активацией иммунокомпетентных клеток, которая, по данным литературы, может сохраняться на клеточном уровне длительное время после перенесенной инфекции [1], а с другой стороны, продолжением влияния ВЭБ-ассоциированных факторов, направленных на сохранение патогена в латентном состоянии.…”

Chronic active Epstein–Barr virus enteritis: A literature review

“…It was first reported by Epstein and Barr in 1964 from malignant lymphoma tissue culture in African children, the infection of which can lead to a variety of benign and malignant lymphoproliferative diseases (LPD) such as infectious mononucleosis (IM), African Burkitt's lymphoma, malignant lymphoma, and hemophagocytic syndrome. Additionally, EBV has been found to play a significant role in different types of malignancies over time, including those of epithelial origin, gastric cancer, oral cancer, and breast cancer 6–10 …”