Related Experiment Video
Updated: May 12, 2026
11:44
A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
Published on: January 24, 2016
12.1K
Reduced IRF4 expression promotes lytic phenotype in Type 2 EBV-infected B cells
Jillian A Bristol1, Joshua Brand1, Makoto Ohashi1
1Department of Oncology, McArdle Laboratory for Cancer Research, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Plos Pathogens
|April 26, 2022
Summary
Type 1 and Type 2 Epstein-Barr virus (EBV) infections in B cells show distinct gene expression profiles. Decreased IRF4 in Type 2 EBV infections contributes to both latent and lytic EBV phenotypes.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Epstein-Barr virus (EBV) exists in two main types, T1 and T2, with differing EBNA2 and EBNA 3A/B/C proteins.
- Type 1 EBV transforms B cells more efficiently than Type 2 EBV in vitro, while Type 2 EBV-infected cells exhibit increased lytic activity.
- Previous research indicated that elevated NFATc1/c2 activity and a specific promoter motif (Zp-V3) in Type 2 EBV strains promote lytic infection.
Purpose of the Study:
- To compare cellular and viral gene expression in lymphoblastoid cell lines (LCLs) infected with either Type 1 or Type 2 EBV strains.
- To elucidate the role of Interferon Regulatory Factor 4 (IRF4) in the differential phenotypes of Type 1 and Type 2 EBV infections.
Main Methods:
- Bulk and single-cell RNA sequencing (RNA-seq) were employed to analyze gene expression differences.
- Gene Set Enrichment Analysis (GSEA) was used to interpret the functional implications of differential gene expression.
- RNA interference (knock-down) and overexpression techniques were utilized to assess the function of IRF4.
Main Results:
- Type 2 EBV-infected LCLs were distinguishable from Type 1 LCLs, with approximately 600 differentially expressed cellular genes.
- GSEA revealed increased B-cell receptor (BCR) signaling, NFAT activation, and epithelial-mesenchymal-transition-associated genes in Type 2 LCLs.
- Type 2 LCLs showed decreased RNA and protein expression of IRF4, a gene crucial for Type 1 LCL survival and a negative regulator of BCR signaling. Knock-down of IRF4 in Type 1 LCLs induced lytic reactivation, while its overexpression inhibited NFAT activity and lytic EBV reactivation.
Conclusions:
- Significant differences exist in cellular gene expression between B cells infected with Type 1 versus Type 2 EBV.
- Reduced IRF4 expression in Type 2 EBV-infected cells contributes to both latent and lytic infection phenotypes.
- IRF4 plays a critical role in modulating EBV infection outcomes, influencing NFAT activation and BCR signaling pathways.
