The regulatory effect and molecular mechanism of Epstein-Barr virus protein LMP-1 in SLE susceptibility gene expression.

The development of systemic lupus erythematosus (SLE) involves both genetic and environmental factors. Epstein-Barr virus (EBV) infection has been implicated in SLE pathogenesis, particularly through the activity of latent membrane protein 1 (LMP-1). This study aimed to explore the role of LMP-1 in regulating susceptibility gene expression in SLE. Peripheral blood mononuclear cells (PBMCs) from SLE patients and H9 T cells were used to investigate this mechanism both in vivo and in vitro. RNA-seq analysis revealed that LMP-1 and the SLE susceptibility gene AT-rich interactive domain 5B (ARID5B) were significantly upregulated in SLE. Overexpression of LMP-1 in H9 T cells further increased ARID5B expression. Histone H3K27 methylation, catalyzed by enhancer of zeste homolog 2 (EZH2), was significantly elevated, suggesting epigenetic modifications play a role in this regulation. H3K27 methylation was studied due to its known involvement in transcriptional repression and chromatin remodeling in autoimmune diseases. Furthermore, phosphorylated p65 (p-p65), a marker of nuclear factor-kappa-B (NF-κB) pathway activation, was increased. Blocking the NF-κB signaling pathway reduced ARID5B expression, indicating that LMP-1 may regulate susceptibility genes through NF-κB signaling and histone modifications. These findings suggest that EBV LMP-1 contributes to SLE pathogenesis by epigenetically modulating susceptibility gene expression and activating inflammatory pathways. Copyright © 2025. Published by Elsevier B.V.

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Xiang Zhang, Shouci Hu, Puchang Luo, Zhiyu Li, Zhejun Chen, Cong Xia, Linxuan Fan, Rongqun Li, Hongbo Chen. The regulatory effect and molecular mechanism of Epstein-Barr virus protein LMP-1 in SLE susceptibility gene expression. Immunology letters. 2025 Jun;273:106993

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PMID: 40023262

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