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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,6,24]]},"abstract":"<jats:p>Herpesviruses, including Epstein\u2013Barr virus (EBV) \u2013 a human oncogenic virus and essential trigger of multiple sclerosis \u2013 must bypass host DNA-sensing mechanisms to establish lifelong, latent infection. Therefore, herpesviruses encode viral proteins to disrupt key host factors involved in DNA sensing and viral restriction. The first viral latency protein expressed, EBNA-LP, is essential for transformation of na\u00efve B cells and establishment of viral gene expression, yet its role in evading host defenses remains unclear. Using single-cell RNA sequencing of EBNA-LP Knockout (LPKO)-infected B cells, we reveal an antiviral response landscape implicating the \u201cspeckled proteins\u201d as key cellular restriction factors countered by EBNA-LP. 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