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

Cristina Venturini; Charlotte J Houldcroft; Arina Lazareva; Fanny Wegner; Sofia Morfopoulou; Persis J Amrolia; Zainab Golwala; Anupama Rao; Stephen D Marks; Jacob Simmonds; Tetsushi Yoshikawa; Paul J Farrell; Jeffrey I Cohen; Austen J Worth; Judith Breuer

doi:10.1111/bjh.17790

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

Br J Haematol. 2021 Oct;195(2):249-255. doi: 10.1111/bjh.17790. Epub 2021 Aug 24.

Authors

Cristina Venturini¹, Charlotte J Houldcroft², Arina Lazareva³, Fanny Wegner^{4

5}, Sofia Morfopoulou¹, Persis J Amrolia³, Zainab Golwala⁶, Anupama Rao⁶, Stephen D Marks^{7

8}, Jacob Simmonds⁶, Tetsushi Yoshikawa⁹, Paul J Farrell¹⁰, Jeffrey I Cohen¹¹, Austen J Worth¹², Judith Breuer^{1

6}

Affiliations

¹ Institute of Child Health, University College London, London, UK.
² Department of Medicine, University of Cambridge, Cambridge, UK.
³ Bone Marrow Transplantation Department, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
⁴ Applied Microbiology Research, Department of Biomedicine, University of Basel, Switzerland.
⁵ Clinical Bacteriology and Mycology, University Hospital Basel, Basel, Switzerland.
⁶ Great Ormond Street Hospital for Children NHS Foundation Trust, UK.
⁷ Department of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, UK.
⁸ NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London Great Ormond Street Institute of Child Health, London, UK.
⁹ Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Japan.
¹⁰ Section of Virology, Department of Infectious Disease, Imperial College Faculty of Medicine, London, UK.
¹¹ Laboratory of Infectious Disease, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.
¹² Department of Immunology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.

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.

Keywords: Epstein-Barr virus; chronic active EBV; defective viral genome.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Asia, Eastern / epidemiology
Biomarkers / analysis
Case-Control Studies
Child
Child, Preschool
Chronic Disease
Defective Viruses / genetics
Epstein-Barr Virus Infections / blood*
Epstein-Barr Virus Infections / drug therapy
Epstein-Barr Virus Infections / epidemiology
Female
Herpesvirus 4, Human / genetics*
Humans
Immunologic Factors / therapeutic use
Male
Peripheral Blood Stem Cell Transplantation / methods
Polymorphism, Single Nucleotide / genetics
Rituximab / therapeutic use
Saliva / metabolism*
Sequence Deletion / genetics*
Treatment Outcome
Virus Replication / genetics

Substances

Biomarkers
Immunologic Factors
Rituximab

Abstract

Publication types

MeSH terms

Substances

Grants and funding