Induction of Epstein-Barr virus (EBV) lytic cycle in vitro causes oxidative stress in lymphoblastoid B cell lines

Gargouri, Bilel; Pelt, Jos van; Feki, Amal; Attia, Hammadi; Lassoued, Saloua

doi:10.1007/s11010-008-9984-1

Cited by 28 publications

(29 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The autophagy machinery probably degrades cellular or viral factors that repress EBV lytic reactivation. Additionally, the induction of the EBV lytic cycle causes endoplasmic reticulum and oxidative stresses (71), and autophagic induction may prevent stress-induced cell death, eventually favoring lytic development. This study also found that 3-MA, an inhibitor of autophagy, led to viral particles being retained within cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Autophagic Activation by Rta of Epstein-Barr Virus via the Extracellular Signal-Regulated Kinase Pathway

Hung

Chen

Wang

et al. 2014

J Virol

View full text Add to dashboard Cite

Autophagy is an intracellular degradation pathway that provides a host defense mechanism against intracellular pathogens. However, many viruses exploit this mechanism to promote their replication. This study shows that lytic induction of EpsteinBarr virus (EBV) increases the membrane-bound form of LC3 (LC3-II) and LC3-containing punctate structures in EBV-positive cells. Transfecting 293T cells with a plasmid that expresses Rta also induces autophagy, revealing that Rta is responsible for autophagic activation. The activation involves Atg5, a key component of autophagy, but not the mTOR pathway. The expression of Rta also activates the transcription of the genes that participate in the formation of autophagosomes, including LC3A, LC3B, and ATG9B genes, as well as those that are involved in the regulation of autophagy, including the genes TNF, IRGM, and TRAIL. Additionally, treatment with U0126 inhibits the Rta-induced autophagy and the expression of autophagy genes, indicating that the autophagic activation is caused by the activation of extracellular signal-regulated kinase (ERK) signaling by Rta. Finally, the inhibition of autophagic activity by an autophagy inhibitor, 3-methyladenine, or Atg5 small interfering RNA, reduces the expression of EBV lytic proteins and the production of viral particles, revealing that autophagy is critical to EBV lytic progression. This investigation reveals how an EBV-encoded transcription factor promotes autophagy to affect viral lytic development. IMPORTANCEAutophagy is a cellular process that degrades and recycles nutrients under stress conditions to promote cell survival. Although autophagy commonly serves as a defense mechanism against viral infection, many viruses exploit this mechanism to promote their replication. This study finds that a transcription factor that is encoded by Epstein-Barr virus (EBV), Rta, activates autophagy, and the inhibition of autophagy reduces the ability of the virus to express viral lytic proteins and to generate progeny. Unlike other virus-encoded proteins that modulate autophagy by interacting with proteins that are involved in the autophagic pathway, Rta activates the transcription of the autophagy-related genes via the ERK pathway. The results of this study reveal how the virus manipulates autophagy to promote its lytic development.

show abstract

Section: Discussionmentioning

confidence: 99%

Regulation of Autophagic Activation by Rta of Epstein-Barr Virus via the Extracellular Signal-Regulated Kinase Pathway

Hung

Chen

Wang

et al. 2014

J Virol

View full text Add to dashboard Cite

show abstract

“…Oxidative stress activates the EBV early gene BZLF-1, which causes the reactivation of EBV lytic cycle [114]. This has been proposed to play an important role in the pathogenesis of EBV-associated diseases including malignant transformations [115, 116]. …”

Section: Viruses Cause Oxidative Stress In Host Cellsmentioning

confidence: 99%

Viruses as Modulators of Mitochondrial Functions

Anand

Tikoo

2013

Advances in Virology

125

113

View full text Add to dashboard Cite

Mitochondria are multifunctional organelles with diverse roles including energy production and distribution, apoptosis, eliciting host immune response, and causing diseases and aging. Mitochondria-mediated immune responses might be an evolutionary adaptation by which mitochondria might have prevented the entry of invading microorganisms thus establishing them as an integral part of the cell. This makes them a target for all the invading pathogens including viruses. Viruses either induce or inhibit various mitochondrial processes in a highly specific manner so that they can replicate and produce progeny. Some viruses encode the Bcl2 homologues to counter the proapoptotic functions of the cellular and mitochondrial proteins. Others modulate the permeability transition pore and either prevent or induce the release of the apoptotic proteins from the mitochondria. Viruses like Herpes simplex virus 1 deplete the host mitochondrial DNA and some, like human immunodeficiency virus, hijack the host mitochondrial proteins to function fully inside the host cell. All these processes involve the participation of cellular proteins, mitochondrial proteins, and virus specific proteins. This review will summarize the strategies employed by viruses to utilize cellular mitochondria for successful multiplication and production of progeny virus.

show abstract

“…There is evidence that viral infections (hepatitis C, HIV and influenza) are associated with an increased production of ROS and that could be involved in the pathogenesis [33,34]. EBV infection is also associated with the production of ROS [35,36] and this has been reported in EBV-associated diseases such as Burkitt’s lymphoma and NPC [37,38]. These studies imply that ROS are incriminated in EBV-associated disease.…”

Section: Introductionmentioning

confidence: 99%

Reactive Oxygen Species Mediate Epstein-Barr Virus Reactivation by N-Methyl-N’-Nitro-N-Nitrosoguanidine

Huang

Fang

et al. 2013

PLoS ONE

View full text Add to dashboard Cite

N-nitroso compounds (NOCs) and Epstein-Barr virus (EBV) reactivation have been suggested to play a role in the development of nasopharyngeal carcinoma (NPC). Although chemicals have been shown to be a risk factor contributing to the carcinogenesis of NPC, the underlying mechanism is not fully understood. We demonstrated recently that N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) enhances the genomic instability and tumorigenicity of NPC cells via induction of EBV reactivation. However, the mechanisms that trigger EBV reactivation from latency remain unclear. Here, we address the role of ROS in induction of EBV reactivation under MNNG treatment. EBV reactivation was induced in over 70% of EBV-positive NA cells and the promoter of Rta (Rp) was activated after MNNG treatment. Inhibitor experiments revealed ATM, p38 MAPK and JNK were activated by ROS and involved in MNNG-induced EBV reactivation. Significantly, ROS scavengers N-acetyl-L-cysteine (NAC), catalase and reduced glutathione inhibited EBV reactivation under MNNG and H2O2 treatment, suggesting ROS mediate EBV reactivation. The p53 was essential for EBV reactivation and the Rp activation by MNNG. Moreover, the p53 was phosphorylated, translocated into nucleus, and bound to Rp following ROS stimulation. The results suggest ROS play an important role in initiation of EBV reactivation by MNNG through a p53-dependent mechanism. Our findings demonstrate novel signaling mechanisms used by NOCs to induce EBV reactivation and provide a novel insight into NOCs link the EBV reactivation in the contribution to the development of NPC. Notably, this study indicates that antioxidants might be effective for inhibiting N-nitroso compound-induced EBV reactivation and therefore could be promising preventive and therapeutic agents for EBV reactivation-associated malignancies.

show abstract

Induction of Epstein-Barr virus (EBV) lytic cycle in vitro causes oxidative stress in lymphoblastoid B cell lines

Cited by 28 publications

References 53 publications

Regulation of Autophagic Activation by Rta of Epstein-Barr Virus via the Extracellular Signal-Regulated Kinase Pathway

Regulation of Autophagic Activation by Rta of Epstein-Barr Virus via the Extracellular Signal-Regulated Kinase Pathway

Viruses as Modulators of Mitochondrial Functions

Reactive Oxygen Species Mediate Epstein-Barr Virus Reactivation by N-Methyl-N’-Nitro-N-Nitrosoguanidine

Contact Info

Product

Resources

About