EBV deletions as biomarkers of response to treatment of Chronic Active Epstein Barr Virus

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Abstract
Chronic active Epstein Barr Virus (CAEBV) is a rare and severe condition occurring in previously healthy individuals associated with persistent EBV viraemia, fever, lymphadenopathy and hepatosplenomegaly. Specific deletions in the EBV genome have been found in CAEBV and certain lymphomas. However, it is unclear how stable these deletions are, whether they are present in different sites and how they evolve in response to treatment. We sequenced fifteen longitudinal blood samples from three CAEBV patients, comparing the results with 13 saliva samples from CAEBV patients and sequences from benign (both primary infection and reactivation) and malignant EBV-related conditions. We observed large EBV deletions in blood, some of which are predicted to disrupt viral replication, but not saliva from patients with CAEBV. Deletions were stable over time but were lost following successful peripheral blood stem cell transplants (PBSCT) or in one case, treatment with rituximab. Our results are consistent with the likelihood that certain deletions occurring in virus from patients with CAEBV are associated with the evolution and persistence of haematological clones. We propose that the loss of EBV deletions following successful treatment should be investigated as a potential biomarker to aid management of CAEBV. Key points Unique EBV deletions are found in European CAEBV patients. Loss of deletions occurs following effective treatment and may prove useful in the management of disease.
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