Therapeutic Strategies against Epstein-Barr Virus-Associated Cancers Using Proteasome Inhibitors

Viruses. 2017 Nov 21;9(11):352. doi: 10.3390/v9110352.

Abstract

Epstein-Barr virus (EBV) is closely associated with several lymphomas (endemic Burkitt lymphoma, Hodgkin lymphoma and nasal NK/T-cell lymphoma) and epithelial cancers (nasopharyngeal carcinoma and gastric carcinoma). To maintain its persistence in the host cells, the virus manipulates the ubiquitin-proteasome system to regulate viral lytic reactivation, modify cell cycle checkpoints, prevent apoptosis and evade immune surveillance. In this review, we aim to provide an overview of the mechanisms by which the virus manipulates the ubiquitin-proteasome system in EBV-associated lymphoid and epithelial malignancies, to evaluate the efficacy of proteasome inhibitors on the treatment of these cancers and discuss potential novel viral-targeted treatment strategies against the EBV-associated cancers.

Keywords: Epstein-Barr virus; Epstein-Barr virus nuclear antigen (EBNA)-3C; apoptosis; cell cycle; lytic reactivation; proteasome inhibitor.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Burkitt Lymphoma / drug therapy
  • Burkitt Lymphoma / virology
  • Carcinoma / drug therapy
  • Carcinoma / virology
  • Epstein-Barr Virus Infections / complications
  • Epstein-Barr Virus Infections / drug therapy*
  • Epstein-Barr Virus Infections / virology
  • Epstein-Barr Virus Nuclear Antigens
  • Herpesvirus 4, Human / pathogenicity
  • Hodgkin Disease / drug therapy
  • Hodgkin Disease / virology
  • Humans
  • Lymphoma / drug therapy*
  • Lymphoma / virology
  • Mice
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / drug therapy
  • Nasopharyngeal Neoplasms / virology
  • Proteasome Endopeptidase Complex / drug effects*
  • Proteasome Inhibitors / administration & dosage
  • Proteasome Inhibitors / therapeutic use*
  • Ubiquitin / drug effects

Substances

  • Epstein-Barr Virus Nuclear Antigens
  • Proteasome Inhibitors
  • Ubiquitin
  • Proteasome Endopeptidase Complex