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Unstable EBV latency drives inflammation in multiple sclerosis patient derived spontaneous B cells [EBV WGS]

ABSTRACT: Epstein-Barr virus (EBV) is an etiologic risk factor, and likely prerequisite, for the development of multiple sclerosis (MS). However, the role of EBV infected B cells in the immunopathology of MS is not well understood. Here, we characterized spontaneous lymphoblastoid cell lines (SLCLs) isolated from MS patients and healthy controls (HC) ex vivo to study EBV and host gene expression in the context of an individual’s endogenous EBV. SLCLs derived from MS patient B cells during active disease had higher EBV lytic gene expression than SLCLs from MS patients with stable disease or HCs. Host gene expression analysis revealed activation of pathways associated with hypercytokinemia and interferon signaling in MS SLCLs and differential expression of several genes, including upregulation of forkhead box protein 1 (FOXP1), which contributes to EBV lytic gene expression. In addition, we demonstrate that antiviral approaches targeting EBV replication decreased inflammatory cytokine production and diminished autologous CD4+ T cell responses. These data suggest that dysregulation of intrinsic B-cell control of EBV gene expression drives a pro-inflammatory, pathogenic B cell phenotype that can be attenuated by suppressing EBV lytic gene expression.

ORGANISM(S): human gammaherpesvirus 4

PROVIDER: GSE221624 | GEO | 2023/12/21

REPOSITORIES: GEO

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