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ISG15-Mediated Suppression of Type I Interferon Signaling Leads to Susceptibility to Epstein-Barr Virus Infection (Early_Infection_day7_BulkRNAseq)

GSE298096 Homo sapiens Expression profiling by high throughput sequencing 9 samples Submitted 2025/05/29 Platform GPL34284
Summary
Epstein-Barr Virus (EBV), the first identified human oncogenic virus, is linked to numerous malignancies, including gastric cancer, nasopharyngeal cancer and multiple B-cell Lymphomas. However, the host-virus interactions that regulate EBV-driven cell transformation and pathogenesis remain incompletely understood. Here, employing a Cas9–ribonucleoprotein (RNP)-based screen in primary B cells, we identified 11 host factors that promote and 35 that restrict EBV-driven outgrowth. Notably, ISG15, a ubiquitin-like, type I interferon-induced antiviral protein, exhibited a dependency role for growth in early stages of infection but not in LCLs. Mechanistically, we found that the regulation of free ISG15 levels greatly impacts the proliferation capacity of EBV-infected B-cells, by modulating the activation of type I IFN signaling. Finally, we identified rare germ-line variants in UBA7, the ISG15 E1 enzyme, in patients with EBV severe disorders, that impair the ISG15 conjugation process. This highlights a critical role of ISG15 in the control of EBV infections.
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Direct links to NCBI, no account and no request form: the whole study as GSE298096_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 9 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1268347 and SRA study SRP588454. Searching any of these in the dataset finder brings you back here.

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