Effect of transforming growth factor-beta1 on the cell growth and Epstein-Barr virus reactivation in EBV-infected epithelial cell lines

Virology. 2001 Sep 15;288(1):109-18. doi: 10.1006/viro.2001.1071.


Transforming growth factor (TGF)-beta1 is a multifunctional cytokine that plays important roles in regulating cell growth and differentiation in many biological systems. In this study, we found that gastric tissue-derived Epstein-Barr virus (EBV)-infected epithelial cell lines GT38 and GT39 had resistance to TGF-beta1-mediated growth inhibition and apoptosis compared to a TGF-beta1-susceptible gastric carcinoma cell line HSC-39. However, TGF-beta1 partially induced EBV reactivation in GT38 and GT39 cells, as shown by the induction of EBV immediate-early BZLF1 RNA and its protein product ZEBRA and early antigen-D. The expressions of TGF-beta receptor I and II were detected in GT38 and GT39 cells by Northern and Western blot analyses. Both cell lines spontaneously produced the TGF-beta1, which was sufficient for inhibiting cell growth of HSC-39 cells. Taken together, these data suggest that TGF-beta1 may be a key factor for EBV reactivation and selective growth of EBV-infected epithelial cells in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activin Receptors, Type I*
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Cell Division / drug effects*
  • Cell Line
  • DNA-Binding Proteins / genetics
  • Epithelial Cells
  • Flow Cytometry
  • Gastric Mucosa
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation, Viral / drug effects
  • Herpesvirus 4, Human / drug effects*
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / physiology
  • Humans
  • Protein-Serine-Threonine Kinases / genetics
  • RNA, Viral / genetics
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / genetics
  • Stomach Neoplasms
  • Trans-Activators / genetics
  • Transcription, Genetic / drug effects*
  • Transforming Growth Factor beta / pharmacology*
  • Tumor Cells, Cultured
  • Viral Proteins / genetics
  • Virus Activation / drug effects


  • BZLF1 protein, Herpesvirus 4, Human
  • DNA-Binding Proteins
  • RNA, Viral
  • Receptors, Transforming Growth Factor beta
  • Trans-Activators
  • Transforming Growth Factor beta
  • Viral Proteins
  • Protein-Serine-Threonine Kinases
  • Activin Receptors, Type I
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II