Epstein-Barr virus induces an oxidative stress during the early stages of infection in B lymphocytes, epithelial, and lymphoblastoid cell lines

Abstract

The study investigates the direct effect of Epstein-Barr virus infection on the oxidative profile of in vitro cultivated human cells. For this purpose, a panel of human EBV target cells presenting heterogeneity in their cellular and culture types (epithelial cells or lymphocytes; primary culture or continuous cell culture) was selected. These cells are purified human B lymphocytes, DG75, 293, and HepG2 cell lines. The oxidative stress was evaluated during the early stages of infection (2, 12, and 24 h) by measuring malondialdehyde, the end product of the lipid peroxidation, as well as the activities of two antioxidant enzymes: catalase and superoxide dismutase. The obtained results were compared with those of the untreated cells and the K562 cell line which has no interaction with EBV. The incubation of the different target cells with EBV induced an oxidative stress in the purified B lymphocytes, DG75, and 293, but not in HepG2 and K562. This oxidative stress was highlighted by an increase in MDA level (P < 0.05), which began 2 h after the addition of the virus and persisted after 12 and 24 h. Simultaneously, a decrease in catalase and superoxide dismutase activities was observed (P < 0.05), suggesting an alteration of the molecular mechanisms promoting cellular resistance to reactive oxygen species (ROS). The efficiency of EBV infection, assessed by viral DNA PCR amplification, was confirmed in 293 and DG75 but not in HepG2, which was in total concordance with their oxidative profiles. In conclusion, the EBV infection of B and epithelial cells leads to the establishment of an oxidative stress which can play a key role during the viral transformation.

Changes in the Nasopharyngeal Carcinoma Nuclear Proteome Induced by the EBNA1 Protein of Epstein-Barr Virus Reveal Potential Roles for EBNA1 in Metastasis and Oxidative Stress Responses

“…These observations are consistent with those of Gruhne et al (20), who found that EBNA1 increased ROS and NOX2 levels in B cells. In addition, primary EBV infection has been shown to increase oxidative stress in B cells, epithelial cells, and lymphoblastoid cell lines (30), as well as in EBV-positive tumor cells (5,10). In contrast to our results, Gruhne et al (20) reported that EBNA1 did not affect ROS or NOX2 transcripts in epithelial cells.…”

The Epstein–Barr virus nuclear antigen-1 promotes genomic instability via induction of reactive oxygen species

“…Earlier studies have reported increased levels of ROS during primary EBV infection (26) and in EBV-carrying tumor cells (18,19), attributing this effect to virion-mediated triggering of the CR2 receptor (27), induction of IL-10 by the viral EBV-encoded, untranslated RNAs (EBERs) (18), or induction of lipoxygenases by unknown viral genes (19). Although it is possible that EBV might have evolved different strategies for inducing ROS during different phases of the infection, the selective up-regulation of NOX2 and activation of the NADPH oxidase in EBNA-1-positive B cells suggest a pivotal role of ROS in growth transformation.…”

Reactive Oxygen Species Are Induced by Kaposi's Sarcoma-Associated Herpesvirus Early during Primary Infection of Endothelial Cells To Promote Virus Entry

“…Herpes simplex virus 2 (HSV-2) induced a 1.5-to 2-fold increase in ROS production 1 h after the infection of RAW 264.7 cells (64). Similarly, the gamma-1 herpesvirus Epstein-Barr virus (EBV) induced oxidative stress during the early stages of primary infections in B lymphocytes and epithelial and lymphoblastic cell lines (65). In this study, a 2-fold increase in malondialdehyde activity, indicative of lipid peroxidation, was measured.…”