This landmark 2010 study was the first to identify a surprising detail about how Epstein-Barr virus (EBV) behaves in adults with EBV-HLH: rather than hiding mainly in T cells, as seen in most previous cases, the virus was found in unusually high levels within natural killer (NK) cells.

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Researchers at the University of Birmingham studied three adult patients diagnosed with EBV-HLH between 2007 and 2009. All three met the established clinical criteria for the condition, presenting with fever, an enlarged spleen, and evidence of hemophagocytosis (immune cells abnormally consuming blood cells). Using cell-sorting techniques, the team isolated different types of immune cells from each patient's blood and measured how much EBV was present in each.

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What they found:

• In all three patients, NK cells carried far higher levels of EBV than T cells or B cells — a pattern not previously reported in adult EBV-HLH cases.
• Despite this, NK cells made up only a small fraction (2–5%) of each patient's total white blood cells, showing that even a small infected population can drive severe disease.
• All three patients had evidence of previous EBV exposure, rather than a first-time infection — challenging the assumption that EBV-HLH mainly strikes during primary infection.
• Outcomes varied significantly: two patients died despite treatment, while the third — who also had co-existing Hodgkin lymphoma — achieved a complete response to chemotherapy.

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Why it matters:

This research helped shift scientific understanding of EBV-HLH, showing that the virus can target different immune cells than previously thought, and that the disease isn't limited to first-time infections. The authors also highlighted how easily EBV-HLH can be missed or diagnosed late, because its early symptoms resemble many other infections. Their findings support the case for greater awareness of EBV-HLH in adults and for further research into which immune cells the virus infects, as a step toward more targeted treatment.