Genome diversity of Epstein-Barr virus from multiple tumor types and normal infection

Autor: Alan B. Rickinson, Simon J. Watson, Samantha Correia, Martin J. Allday, Craig Corton, Anne L. Palser, Mohammed M. Ba Abdullah, Paul J. Farrell, Lawrence S. Young, Paul Kellam, Paul Murray, John R. Arrand, Nicholas E. Grayson, Robert E. White, Matthew Cotten
Přispěvatelé: Imperial College Trust, King Abdulaziz City for Science and Technology (KA
Jazyk: angličtina
Rok vydání: 2015
Předmět:
SELECTION
Epstein-Barr Virus Infections
Herpesvirus 4
Human
Epitopes
T-Lymphocyte
medicine.disease_cause
Genome
hemic and lymphatic diseases
PHYLOGENIES
Antigens
Viral
11 Medical and Health Sciences
Phylogeny
Genetics
Recombination
Genetic
education.field_of_study
ALGORITHMS
3. Good health
AMINO-ACID
Carrier State
Life Sciences & Biomedicine
Immunology
Population
BIOLOGY
Single-nucleotide polymorphism
Genome
Viral
Biology
Microbiology
INTERTYPIC RECOMBINANTS
SEQUENCE
Polymorphism
Single Nucleotide
Virus
Viral Matrix Proteins
Virology
07 Agricultural and Veterinary Sciences
Cell Line
Tumor
Genetic variation
medicine
Humans
Amino Acid Sequence
education
Gene
QR355
CHINESE POPULATION
TOOLS
Science & Technology
STRAINS
Genetic Variation
LYMPHOMAGENESIS
06 Biological Sciences
Epstein–Barr virus
Human genetics
INDIVIDUALS
Genetic Diversity and Evolution
Epstein-Barr Virus Nuclear Antigens
Insect Science
DNA
Viral
Zdroj: Journal of Virology
ISSN: 0022-538X
Popis: Epstein-Barr virus (EBV) infects most of the world's population and is causally associated with several human cancers, but little is known about how EBV genetic variation might influence infection or EBV-associated disease. There are currently no published wild-type EBV genome sequences from a healthy individual and very few genomes from EBV-associated diseases. We have sequenced 71 geographically distinct EBV strains from cell lines, multiple types of primary tumor, and blood samples and the first EBV genome from the saliva of a healthy carrier. We show that the established genome map of EBV accurately represents all strains sequenced, but novel deletions are present in a few isolates. We have increased the number of type 2 EBV genomes sequenced from one to 12 and establish that the type 1/type 2 classification is a major feature of EBV genome variation, defined almost exclusively by variation of EBNA2 and EBNA3 genes, but geographic variation is also present. Single nucleotide polymorphism (SNP) density varies substantially across all known open reading frames and is highest in latency-associated genes. Some T-cell epitope sequences in EBNA3 genes show extensive variation across strains, and we identify codons under positive selection, both important considerations for the development of vaccines and T-cell therapy. We also provide new evidence for recombination between strains, which provides a further mechanism for the generation of diversity. Our results provide the first global view of EBV sequence variation and demonstrate an effective method for sequencing large numbers of genomes to further understand the genetics of EBV infection. IMPORTANCE Most people in the world are infected by Epstein-Barr virus (EBV), and it causes several human diseases, which occur at very different rates in different parts of the world and are linked to host immune system variation. Natural variation in EBV DNA sequence may be important for normal infection and for causing disease. Here we used rapid, cost-effective sequencing to determine 71 new EBV sequences from different sample types and locations worldwide. We showed geographic variation in EBV genomes and identified the most variable parts of the genome. We identified protein sequences that seem to have been selected by the host immune system and detected variability in known immune epitopes. This gives the first overview of EBV genome variation, important for designing vaccines and immune therapy for EBV, and provides techniques to investigate relationships between viral sequence variation and EBV-associated diseases.
Databáze: OpenAIRE
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