title: The genetic diversity of Epstein-Barr virus in the setting of transplantation relative to non-transplant settings: A feasibility study.
abstract: This study examines EBV strains from transplant patients and patients with IM by sequencing major EBV genes. We also used NGS to detect EBV DNA within total genomic DNA, and to evaluate its genetic variation. Sanger sequencing of major EBV genes was used to compare SNVs from samples taken from transplant patients vs. patients with IM. We sequenced EBV DNA from a healthy EBV-seropositive individual on a HiSeq 2000 instrument. Data were mapped to the EBV reference genomes (AG876 and B95-8). The number of EBNA2 SNVs was higher than for EBNA1 and the other genes sequenced within comparable reference coordinates. For EBNA2, there was a median of 15 SNV among transplant samples compared with 10 among IM samples (p = 0.036). EBNA1 showed little variation between samples. For NGS, we identified 640 and 892 variants at an unadjusted p value of 5 × 10(-8) for AG876 and B95-8 genomes, respectively. We used complementary sequence strategies to examine EBV genetic diversity and its application to transplantation. The results provide the framework for further characterization of EBV strains and related outcomes after organ transplantation.
authors.affiliation: Division of Infectious Diseases, Department of Paediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.|Research Institute, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.|The Transplant and Regenerative Medicine Centre, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
authors.forename: Upton D
authors.initials: UD
authors.lastname: Allen
authors.affiliation: The Centre for Applied Genomics, Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Pingzhao
authors.initials: P
authors.lastname: Hu
authors.affiliation: The Centre for Applied Genomics, Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Sergio L
authors.initials: SL
authors.lastname: Pereira
authors.affiliation: Division of Infectious Diseases, Department of Paediatrics, Stollery Children's Hospital, Edmonton, AB, Canada.
authors.forename: Joan L
authors.initials: JL
authors.lastname: Robinson
authors.affiliation: The Centre for Applied Genomics, Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Tara A
authors.initials: TA
authors.lastname: Paton
authors.affiliation: Research Institute, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
authors.forename: Joseph
authors.initials: J
authors.lastname: Beyene
authors.affiliation: Research Institute, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
authors.forename: Nasser
authors.initials: N
authors.lastname: Khodai-Booran
authors.affiliation: The Transplant and Regenerative Medicine Centre, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
authors.forename: Anne
authors.initials: A
authors.lastname: Dipchand
authors.affiliation: The Transplant and Regenerative Medicine Centre, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
authors.forename: Diane
authors.initials: D
authors.lastname: Hébert
authors.affiliation: The Transplant and Regenerative Medicine Centre, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
authors.forename: Vicky
authors.initials: V
authors.lastname: Ng
authors.affiliation: The Transplant and Regenerative Medicine Centre, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nalpathamkalam
authors.affiliation: Division of Infectious Diseases, Department of Paediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.|Research Institute, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
authors.forename: Stanley
authors.initials: S
authors.lastname: Read
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004279:DNA, Viral / Q000235:genetics; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics; D005240:Feasibility Studies; D016679:Genome, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D007223:Infant; D007244:Infectious Mononucleosis / Q000821:virology*; D016377:Organ Transplantation / Q000009:adverse effects; D012016:Reference Values; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: D004279:DNA, Viral; C402641:EBNA-2 protein, Human herpesvirus 4; D019309:Epstein-Barr Virus Nuclear Antigens; D014764:Viral Proteins; C417029:EBV-encoded nuclear antigen 1
keywords: Epstein-Barr virus; genetic variation; next-generation sequencing; whole-genome sequencing