Efficient Epstein-Barr Virus Progeny Production Mediated by Cancer-Derived LMP1 and Virally-Encoded microRNAs

Misako Yajima1, Mamiko Miyata2, Kazufumi Ikuta3

  • 1Division of Microbiology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai 983-8536, Japan. yajima@tohoku-mpu.ac.jp.

Microorganisms
|May 5, 2019
PubMed

Insights

Cancer-derived Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) and viral microRNAs (miRNAs) enhance progeny virus production. This synergy contributes to EBV-driven epithelial cancers.

Area of Science:

  • Virology
  • Molecular Biology
  • Cancer Research

Background:

  • Epstein-Barr virus (EBV) genomes exhibit strain heterogeneity, particularly in latent genes.
  • The functional differences of EBV-encoded latent membrane protein 1 (LMP1) between cancer-associated and non-cancerous strains remain unclear.

Purpose of the Study:

  • To investigate the functional differences of cancer-derived LMP1 within the context of the EBV genome.
  • To elucidate the roles of LMP1 and viral microRNAs (miRNAs) in EBV replication and epithelial carcinogenesis.

Main Methods:

  • Utilized bacterial artificial chromosome (BAC)-cloned EBV genomes containing all viral miRNA genes.
  • Stably transfected HEK293 cells with EBV-BAC clones encoding either nasopharyngeal carcinoma (NPC)-derived CAO-LMP1 (LMP1CAO) or prototype B95-8 strain LMP1 (LMP1B95-8).
  • Assessed the generation of stable transformants and progeny virus production, including experiments with deleted viral miRNA genes.

Main Results:

  • EBV-BAC DNA encoding LMP1CAO generated significantly more stable transformants than LMP1B95-8 in HEK293 cells.
  • Stably transfected cells showed highly efficient production of progeny virus.
  • Deletion of viral miRNA genes impaired progeny virus production, indicating a synergistic role with LMP1.

Conclusions:

  • Cancer-derived LMP1 and viral miRNAs are crucial for efficient EBV progeny virus production.
  • This enhanced viral production contributes to EBV-mediated epithelial carcinogenesis.
  • Strain-specific variations in LMP1 and miRNAs play a significant role in EBV pathogenesis.

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