B. Friedenson
Chronic diseases are increasingly linked to a transient viral exposure, yet known mechanisms do not explain how this exposure eventually leads to chronic pathologies in unrelated tissues. Using Epstein-Barr virus (EBV) as a model, I show that diverse EBV-associated diseases arise from epigenetic misprogramming of progenitor cells. These alterations persist independently of active infection and propagate across cell lineages, generating latent vulnerabilities later unmasked by secondary insults. Breast cancer provided an unresolved test case for EBV involvement: invasive tumors carried EBV-like methylation signatures already present in precursor lesions, independent of lymphocytic infiltration. In EBV-associated multiple sclerosis, three independent cohorts (brain, white matter, and blood) each revealed progenitor-cell methylation anomalies at sites shared with breast and classic EBV-associated cancers. Epigenetic vulnerability in progenitor cells thus emerges as a shared mechanism linking fundamentally different diseases, offering a candidate biomarker and a new target for early intervention.