Host control of persistent Epstein–Barr virus infection

Nature

by Axel Schmidt

February 20, 2026

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Host Control of Persistent Epstein–Barr Virus (EBV) Infection: A New Study Explores Genetic and Non-Genetic Factors The study investigates how the human body manages persistent EBV infection, which affects nearly 90-95% of the global population. EBV, a virus linked to autoimmune diseases and cancers, establishes lifelong infections in B cells. While previous research has focused on its association with diseases like multiple sclerosis and rheumatoid arthritis, this study delves into the genetic and non-genetic factors that influence how well the body controls EBV during persistent infection. Using blood-based genome sequence data from over 800,000 participants in two large studies—UK Biobank and All of Us—the researchers identified EBV presence in approximately 16-21% of individuals. They found strong associations between EBV detection and factors such as HIV infection, immunosuppressive drug use, and smoking, which may increase viral load. Genetic analysis revealed significant links at the Major Histocompatibility Complex (MHC), including specific HLA alleles associated with both MHC class I and II. The study also highlighted epistasis—interactions between different HLA alleles—at the ERAP2 locus, suggesting a complex interplay between genetic factors in controlling EBV. Furthermore, individuals with EBV-associated diseases exhibited higher polygenic burdens of certain HLA alleles. For example, multiple sclerosis was linked to MHC class I alleles, while rheumatoid arthritis showed associations with MHC class II alleles. Phenome-wide analyses revealed overlaps between EBV detection and conditions like inflammatory bowel disease, hypothyroidism, and type 1 diabetes. This suggests that EBV may play a broader role in chronic diseases beyond its well-known associations with autoimmune disorders and cancers. The study underscores the importance of understanding EBV’s genetic and immun

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Originally published on Nature on 2/20/2026