New Genome Sequencing Technique Measures Epstein-Barr Virus in Blood

While usually kept under control, the virus is linked to cancers such as Hodgkin’s lymphoma and autoimmune diseases including multiple sclerosis. Exactly how the immune system regulates this persistent infection has remained unclear. Researchers have now developed a novel approach to estimate EBV levels in blood using existing genome sequencing data, uncovering both genetic and lifestyle factors that influence viral control.

Scientists at the University Hospital Bonn (Bonn, Germany) and the University of Bonn (Bonn, Germany) have repurposed large-scale human genome sequencing datasets to indirectly measure EBV viral load. Genome sequencing data are typically generated to analyze human DNA. The team instead searched these datasets for short DNA fragments originating from the EBV genome, referred to as EBV reads. The presence of these reads correlates with higher EBV viral load.

The researchers analyzed genome sequences from 486,315 participants in the UK Biobank and 336,123 participants in the All of Us project. EBV reads were detected in 16.2% and 21.8% of individuals, respectively. Laboratory validation confirmed that individuals with EBV reads had higher viral loads. Using this large-scale measure, the team identified several key associations, including the fact that immunocompromised individuals show increased EBV viral load.

Active smokers had significantly higher EBV reads, suggesting smoking may impair EBV control, potentially through effects on innate immunity. Seasonal variation was observed, with higher EBV levels detected in winter and lower levels in summer. At the genetic level, the strongest association with EBV viral load was found in the major histocompatibility complex (MHC) region, which encodes proteins critical for immune recognition of pathogens.

In addition to the MHC locus, 27 additional genomic regions were linked to EBV load across both biobanks. Some of these genes are known to influence immune function, while others represent newly identified candidates involved in EBV control. The study, published in Nature, also identified genetic overlap between EBV viral load and EBV-associated diseases. In addition to reinforcing links to multiple sclerosis, the findings suggest potential relevance in other conditions, including type 1 diabetes.

This new method enables large-scale investigation of EBV immunity using already available genomic datasets. By transforming human genome sequencing “by-products” into a measure of persistent viral infection, researchers have opened new opportunities to study the mechanisms of EBV control, links between viral load and disease risk and potential therapeutic targets for EBV-associated cancers and autoimmune disorders. The approach also demonstrates how population biobank data can be repurposed to investigate lifelong viral infections at an unprecedented scale.

"Our results serve as a basis for understanding EBV immunity, and they also open up avenues for new mechanistic studies and therapeutic approaches for EBV-associated diseases,” said Prof. Kerstin Ludwig at the University Hospital Bonn. “In a broader sense, our study illustrates how by-products of human genome sequencing data can be used to investigate persistent viral infections."

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