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Epstein-Barr virus (EBV) deletions as biomarkers of response to treatment of chronic active EBV.

ABSTRACT: Chronic active Epstein-Barr virus (CAEBV) disease is a rare condition characterised by persistent EBV infection in previously healthy individuals. Defective EBV genomes were found in East Asian patients with CAEBV. In the present study, we sequenced 14 blood EBV samples from three UK patients with CAEBV, comparing the results with saliva CAEBV samples and other conditions. We observed EBV deletions in blood, some of which may disrupt viral replication, but not saliva in CAEBV. Deletions were lost overtime after successful treatment. These findings are compatible with CAEBV being associated with the evolution and persistence of EBV⁺ haematological clones that are lost on successful treatment.

SUBMITTER: Venturini C

PROVIDER: S-EPMC8589012 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Epstein-Barr virus (EBV) deletions as biomarkers of response to treatment of chronic active EBV.

Venturini Cristina C Houldcroft Charlotte J CJ Lazareva Arina A Wegner Fanny F Morfopoulou Sofia S Amrolia Persis J PJ Golwala Zainab Z Rao Anupama A Marks Stephen D SD Simmonds Jacob J Yoshikawa Tetsushi T Farrell Paul J PJ Cohen Jeffrey I JI Worth Austen J AJ Breuer Judith J

British journal of haematology 20210824 2

Chronic active Epstein-Barr virus (CAEBV) disease is a rare condition characterised by persistent EBV infection in previously healthy individuals. Defective EBV genomes were found in East Asian patients with CAEBV. In the present study, we sequenced 14 blood EBV samples from three UK patients with CAEBV, comparing the results with saliva CAEBV samples and other conditions. We observed EBV deletions in blood, some of which may disrupt viral replication, but not saliva in CAEBV. Deletions were los ...[more]

PMID: 34431085

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Project description:The main target cells for Epstein-Barr virus (EBV) infection and persistence are B lymphocytes, although T and NK cells can also become infected. In this paper, we characterize the EBV present in 21 pediatric and adult patients who were treated in France for a range of diseases that involve infection of T or NK cells. Of these 21 cases, 5 pediatric patients (21%) and 11 adult patients (52%) were of Caucasian origin. In about 30% of the cases, some of the EBV genomes contain a large deletion. The deletions are different in every patient but tend to cluster near the BART region of the viral genome. Detailed investigation of a family in which several members have persistent T or NK cell infection by EBV indicates that the virus genome deletions arise or are selected independently in each individual patient. Genome sequence polymorphisms in the EBV in these T or NK cell diseases reflect the geographic origin of the patient and not a distinct type of EBV (the 21 cases studied included examples of both type 1 and type 2 EBV infection). Using virus produced from type 1 or type 2 EBV genomes cloned in bacterial artificial chromosome (BAC) vectors, we demonstrate infection of T cells in cord blood from healthy donors. Our results are consistent with transient infection of some T cells being part of normal asymptomatic infection by EBV in young children. IMPORTANCE EBV contributes to several types of human cancer. Some cancers and nonmalignant lymphoproliferative diseases involving T or NK cells contain EBV. These diseases are relatively frequent in Japan and China and have been shown sometimes to have deletions in the EBV genome in the disease cells. We identify further examples of deletions within the EBV genome associated with T or NK cell diseases, and we provide evidence that the virus genomes with these deletions are most likely selected in the individual cases, rather than being transmitted between people during infection. We demonstrate EBV infection of cord blood T cells by highly characterized, cloned EBV genomes and suggest that transient infection of T cells may be part of normal asymptomatic infection by EBV in young children.

Dataset Information

Epstein-Barr virus (EBV) deletions as biomarkers of response to treatment of chronic active EBV.

Publications

Epstein-Barr virus (EBV) deletions as biomarkers of response to treatment of chronic active EBV.

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