New method measures Epstein-Barr virus load in blood from 800,000 people

Researchers find a new way to measure EBV in the blood

A new study has discovered a way to use standard human genome sequencing data to measure the viral load of the Epstein-Barr virus (EBV) in a person's blood. The research, published in Nature, analyzed data from over 800,000 people across two major biobanks.

EBV infects about 90-95% of adults worldwide and establishes a lifelong, dormant infection. While usually harmless, it is a known risk factor for several autoimmune diseases and cancers, though the mechanisms are not fully understood.

EBV detection linked to immune status and habits

The team searched for fragments of the EBV genome within human blood cell sequencing data. They found these viral reads in 16.2% of UK Biobank participants and 21.8% of All of Us participants.

The presence of these reads, dubbed EBVread+, correlated with a higher active viral load in the blood. This signal was stronger in individuals with certain conditions or lifestyles:

• People living with HIV
• Those taking immunosuppressive drugs
• Current smokers

Genetic drivers of EBV control identified

A genome-wide analysis revealed that a person's genetics play a major role in controlling EBV levels. The strongest associations were found in the Major Histocompatibility Complex (MHC), a region critical for immune function.

The study identified 54 independent HLA alleles within the MHC that were linked to higher or lower EBV detection. It also found 27 genetic regions outside the MHC that influence viral control.

Notably, researchers observed epistasis—where the effect of one gene depends on another—between specific MHC class I alleles and a gene called ERAP2.

Connecting viral load to autoimmune disease risk

The researchers then investigated whether the genetic burden for higher EBV load overlapped with known genetic risks for EBV-associated diseases. They found a significant polygenic overlap.

For multiple sclerosis, the link was driven by genetic risk concentrated in MHC class I alleles, particularly HLA-A*02:01. For rheumatoid arthritis, the association was tied to MHC class II alleles.

Phenome-wide analysis also showed a genetic link between higher EBV load and other autoimmune conditions:

• Inflammatory bowel disease
• Hypothyroidism
• Type 1 diabetes

A new tool for studying persistent viruses

The study's major finding is methodological. It proves that viral byproducts in human genome sequencing data can serve as a reliable, large-scale proxy for active viral load.

This approach turns a common biomedical data source into a powerful tool for studying persistent viral infections. It could accelerate research into EBV's role in disease and help identify individuals who may benefit from closer monitoring or new therapies.

"This will facilitate investigation and treatment for EBV and other persistent viral infections," the authors concluded, highlighting the potential for this method to be applied beyond just one virus.