Analysis of gene expression differences pre- and post-lytic reactivation of Epstein–Barr virus in Burkitt's lymphoma

Abstract

Aim: This study explores changes in viral and host gene expressions during Epstein–Barr virus lytic reactivation, establishing a bioinformatics foundation for understanding the pathogenesis of Burkitt's lymphoma (BL) and identifying potential therapeutic targets. Methods: We used the data set GSE141220 to assess differentially expressed genes. Subsequent analyses included Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. Hub genes were identified using Cytoscape. Results: Viral gene expression exhibited significant alterations 24 h after treatment with Sodium butyrate (NaB). Upregulated host genes mainly related to the PI3K-Akt and MAPK signaling pathways. Conclusion: Epstein–Barr virus lytic reactivation is likely to involve the activation of the PI3K-Akt and MAPK signaling pathways. Hub genes may serve as therapeutic targets for BL.

Plain language summary

Our study looks at a severe disease known as Burkitt's lymphoma that is linked to a virus called Epstein–Barr Virus. We looked at the genetic makeup of the virus to explore changes that may show why the virus becomes active after a period of inactivity. We hope this will help to identify new ways to diagnose and treat Burkitt's lymphoma.

Article highlights

Background

• Burkitt's lymphoma (BL) is closely linked to Epstein–Barr virus (EBV), with the lytic phase of EBV also potentially playing a crucial role in tumorigenesis.

• This study explores changes in viral and host gene expression during EBV lytic reactivation to understand BL pathogenesis and identify therapeutic targets.

Methods

• Utilized GSE141220 data set to analyze the changes in virus and their host genes in HH514-16 cell line treated with NaB.

• Conducted Gene ontology (GO) functional annotation and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses.

• Identified hub genes using Cytoscape software.

Results

• Viral gene expression was significantly altered 24 h after NaB treatment, with upregulated host genes associated with PI3K-Akt and MAPK signaling pathways.

• Latency genes showed minor changes, while lytic genes exhibited significant increases after 24 and 48 h of NaB treatment.

Discussion

• EBV lytic reactivation impacts both viral and host gene expression, with potential implications for BL pathogenesis.

• Identification of hub genes such as STAT1, EGF and EGFR suggests promising targets for BL therapy.

• Limitations include the need for broader cell line inclusion and increased sample replicates for improved reliability.

Conclusion

• EBV lytic reactivation may be associated with the activation of the PI3K-Akt and MAPK signaling pathways.

• STAT1, EGFR, EGF and other hub genes may serve as potential targets for the diagnosis and therapy of BL.

Keywords: :

• Burkitt's lymphoma
• Epstein–Barr virus
• lytic reactivation
• sodium butyrate

Author contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by ZG. The first draft of the manuscript was written by WL and BL. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Financial disclosure

This work was supported by the Natural Science Foundation of Shandong Province (ZR2020MH302 and ZR2021MC068). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported by the Natural Science Foundation of Shandong Province (ZR2020MH302 and ZR2021MC068).