Evidence of Epstein-Barr virus heterogeneous gene expression in adult lung transplant recipients with posttransplant lymphoproliferative disorder

J Med Virol. 2021 Aug;93(8):5040-5047. doi: 10.1002/jmv.26936. Epub 2021 Mar 25.


Epstein-Barr virus (EBV)-driven posttransplant lymphoproliferative disorder (PTLD) is a serious complication following lung transplant. The extent to which the presence of EBV in PTLD tissue is associated with survival is uncertain. Moreover, whether the heterogeneity in expression of EBV latency programs is related to the timing of PTLD onset remains unexplored. We retrospectively performed a comprehensive histological evaluation of EBV markers at the tissue level in 34 adult lung transplant recipients with early- and late-onset PTLD. Early-onset PTLD, occurring within the first 12 months posttransplant, had higher odds to express EBV markers. The presence of EBV in PTLD was not associated with a difference in survival relative to EBV-negative tumors. However, we found evidence of heterogeneous expression of EBV latency programs, including type III, IIb, IIa, and 0/I. Our study suggests that the heterogeneous expression of EBV latency programs may represent a mechanism for immune evasion in patients with PLTD after lung transplants. The recognition of multiple EBV latency programs can be used in personalized medicine in patients who are nonresponsive to traditional types of chemotherapy and can be potentially evaluated in other types of solid organ transplants.

Keywords: EBV latency program; Epstein-Barr virus; PTLD; PTLD survival; lung transplant.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Epstein-Barr Virus Infections / etiology
  • Epstein-Barr Virus Infections / mortality
  • Epstein-Barr Virus Infections / virology*
  • Female
  • Gene Expression
  • Herpesvirus 4, Human / genetics*
  • Humans
  • Lung / metabolism
  • Lung / surgery
  • Lung / virology*
  • Lymphoproliferative Disorders / etiology
  • Lymphoproliferative Disorders / mortality
  • Lymphoproliferative Disorders / virology*
  • Male
  • Middle Aged
  • Organ Transplantation / adverse effects*
  • Organ Transplantation / mortality
  • Retrospective Studies
  • Transplant Recipients
  • Viral Proteins / genetics
  • Viral Proteins / metabolism
  • Virus Latency / genetics


  • Viral Proteins