Analysis of Epstein-Barr virus (EBV) genomic variations in EBV-associated lymphoproliferative diseases

Dr Chiang, Alan Kwok Shing   (Principal Investigator (PI))

Dr Hui Kwai Fung   (Co-Investigator)

42

2020-08-01

1487668

Analysis of Epstein-Barr virus (EBV) genomic variations in EBV-associated lymphoproliferative diseases

Epstein-Barr virus, Genomic variation, Infectious monocleosis, Lymphoproliferative diseases, Next-generation sequencing, Post-transplant lymphoproliferative disease

Others - Medicine, Dentistry and Health

19180382

Health and Medical Research Fund - Full Grant

2019

On-going

Epstein-Barr virus (EBV) is a gamma herpesvirus which infects more than 90% of the world’s population. Its infection would lead to infectious mononucleosis (IM), post-transplant lymphoproliferative disorder (PTLD), hemophagocytic lymphohistiocytosis (HLH), several types of lymphomas and epithelial malignancies such as nasopharyngeal carcinoma (NPC). However, the role of EBV genetic variations in the pathogenesis of these EBV-associated diseases remains largely unknown. We had previously compared the whole EBV genomes harboured in 62 NPC patients and 142 population carriers of Hong Kong and reported the presence of high risk EBV variants with particular pathogenic mutations in 97% NPC patients and 40% population carriers. Our preliminary data on EBV genomes derived from 8 IM, 8 PTLD and 5 HLH patients indicated the presence of non-synonymous mutations and small intragenic deletions in EBV lytic (BOLF1, BORF2 and BLLF1) and latent (EBNA3A and EBNA3C) genes. In this proposal, we hypothesize that EBV genetic variations can be associated with the pathogenesis of IM, PTLD and HLH in Hong Kong. We will first sequence the EBV genomes harboured in the saliva, plasma and peripheral blood mononuclear cells of 50 IM, 25 PTLD and 25 HLH patients and saliva of 25 asymptomatic children. We will then analyze the disease-associated variations at strain, haplotype and signal genetic variation levels in the EBV genomes harboured in the patients versus control carriers. The intercompartmental variations between the EBV genomes in different tissue compartments in each patient will also be analyzed to determine the tropism of the disease-associated virus variants.