Interleukin-21 Regulates Expression of Key Epstein-Barr Virus Oncoproteins, EBNA2 and LMP1, in Infected Human B Cells

Virology. 2008 Apr 25;374(1):100-13. doi: 10.1016/j.virol.2007.12.027. Epub 2008 Jan 28.

Abstract

Epstein-Barr virus (EBV) persists for the life of the host by accessing the long-lived memory B cell pool. It has been proposed that EBV uses different combinations of viral proteins, known as latency types, to drive infected B cells to make the transition from resting B cells to memory cells. This process is normally antigen-driven. A major unresolved question is what factors coordinate expression of EBV latency proteins. We have recently described novel type III latency EBV+ B cell lines (OCI-BCLs) that were induced to differentiate into late plasmablasts/early plasma cells in culture with interleukin-21 (IL-21), mimicking normal B cell development. The objective of this study was to determine whether IL-21-mediated signals also regulate the expression of key EBV latent proteins during this window of development. Here we show that IL-21-reduced gene and protein expression of growth-transforming EBV nuclear antigen 2 (EBNA2) in OCI-BCLs. By contrast, the expression of CD40-like, latent membrane protein 1 (LMP1) strongly increased in these cells suggesting an EBNA2-independent mode of regulation. Same results were also observed in Burkitt's lymphoma line Jijoye and B95-8 transformed lymphoblastoid cell lines. The effect of IL-21 on EBNA2 and LMP1 expression was attenuated by a pharmacological JAK inhibitor indicating involvement of JAK/STAT signalling in this process. Our study also shows that IL-21 induced transcription of ebna1 from the viral Q promoter (Qp).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / virology*
  • Cell Line
  • Epstein-Barr Virus Nuclear Antigens / biosynthesis*
  • Gene Expression Regulation, Viral
  • Herpesvirus 4, Human / physiology*
  • Humans
  • Interleukins / physiology*
  • Oncogene Proteins, Viral / biosynthesis*
  • Viral Matrix Proteins / biosynthesis*
  • Viral Proteins / biosynthesis*

Substances

  • EBNA-2 protein, Human herpesvirus 4
  • EBV-associated membrane antigen, Epstein-Barr virus
  • Epstein-Barr Virus Nuclear Antigens
  • Interleukins
  • Oncogene Proteins, Viral
  • Viral Matrix Proteins
  • Viral Proteins
  • interleukin-21
  • EBV-encoded nuclear antigen 1