Epstein-Barr virus genetic variation in lymphoblastoid cell lines derived from Kenyan pediatric population.
Epstein-Barr virus (EBV) is associated with Burkitt's lymphoma (BL), and in regions of sub-Saharan Africa where endemic BL is common, both the EBV Type 1 (EBV-1) and EBV Type 2 strains (EBV-2) are found. Little is known about genetic variation of EBV strains in areas of sub-Saharan Africa. In the present study, spontaneous lymphoblastoid cell lines (LCLs) were generated from samples obtained from Kenya. Polymerase chain reaction (PCR) amplification of the EBV genome was done using multiple primers and sequenced by next-generation sequencing (NGS). Phylogenetic analyses against the published EBV-1 and EBV-2 strains indicated that one sample, LCL10 was closely related to EBV-2, while the remaining 3 LCL samples were more closely related to EBV-1. Moreover, single nucleotide polymorphism (SNP) analyses showed clustering of LCL variants. We further show by analysis of EBNA-1, BLLF1, BPLF1, and BRRF2 that latent genes are less conserved than lytic genes in these LCLs from a single geographic region. In this study we have shown that NGS is highly useful for deciphering detailed inter and intra-variations in EBV genomes and that within a geographic region different EBV genetic variations can co-exist, the implications of which warrant further investigation. The findings will enhance our understanding of potential pathogenic variants critical to the development and maintenance of EBV-associated malignancies.
Department of Microbiology and Immunology, Upstate Medical University, Syracuse, New York, United States of America.
Kenneth O
KO
Simbiri
Department of Microbiology and Immunology, Upstate Medical University, Syracuse, New York, United States of America.
Nicholas A
NA
Smith
Maseno University, Maseno, Kenya.
Richard
R
Otieno
Department of Microbiology and Immunology, Upstate Medical University, Syracuse, New York, United States of America.
Eric E M
EE
Wohlford
Kenya Medical Research Institute, Kisumu, Kenya.
Ibrahim I
II
Daud
Kenya Medical Research Institute, Kisumu, Kenya.
Sumba P
SP
Odada
Department of Neuroscience and Physiology, Upstate Medical University, Syracuse, New York, United States of America.
Frank
F
Middleton
Department of Microbiology and Immunology, Upstate Medical University, Syracuse, New York, United States of America.
Rosemary
R
Rochford
D002051:Burkitt Lymphoma / Q000150:complications / Q000453:epidemiology / Q000473:pathology / Q000821:virology*; D002460:Cell Line; D002648:Child; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000453:epidemiology / Q000473:pathology / Q000821:virology*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics; D018703:Founder Effect; D015870:Gene Expression; D014644:Genetic Variation; D016679:Genome, Viral; D004854:Herpesvirus 4, Human / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007630:Kenya / Q000453:epidemiology; D008214:Lymphocytes / Q000473:pathology / Q000821:virology*; D010802:Phylogeny; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics
C495488:BPLF1 protein, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D054334:Viral Regulatory and Accessory Proteins; C417029:EBV-encoded nuclear antigen 1