The genetic diversity of Epstein-Barr virus in the setting of transplantation relative to non-transplant settings: A feasibility study

Pediatr Transplant. 2016 Feb;20(1):124-9. doi: 10.1111/petr.12610. Epub 2015 Nov 18.

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.

Keywords: Epstein-Barr virus; genetic variation; next-generation sequencing; whole-genome sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Cohort Studies
  • DNA, Viral / genetics
  • Epstein-Barr Virus Nuclear Antigens / genetics
  • Feasibility Studies
  • Genome, Viral
  • Herpesvirus 4, Human / genetics*
  • Humans
  • Infant
  • Infectious Mononucleosis / virology*
  • Organ Transplantation / adverse effects
  • Reference Values
  • Sequence Analysis, DNA
  • Treatment Outcome
  • Viral Load
  • Viral Proteins / genetics
  • Young Adult

Substances

  • DNA, Viral
  • EBNA-2 protein, Human herpesvirus 4
  • Epstein-Barr Virus Nuclear Antigens
  • Viral Proteins
  • EBV-encoded nuclear antigen 1

Associated data

  • GENBANK/AJ507799.2