Phenotypic knock-out of the latent membrane protein 1 of Epstein-Barr virus by an intracellular single-chain antibody

A. Piché, K. Kasono, F. Johanning, T. J. Curiel, D. T. Curiel

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Epstein-Barr virus (EBV) causes lymphoproliferative diseases in immunocompromised patients and is associated with endemic Burkitt lymphoma, nasopharyngeal carcinoma and some cases of Hodgkin disease. The latent membrane protein 1 (LMP1) of EBV is a transmembrane protein that is essential for the transformation of B lymphocyes. LMP1-mediated up-regulation of Bcl-2 is thought to be an important element in this process. As an approach to explore novel treatments for EBV-associated lymphomas, we constructed a single-chain antibody (sFv) directed against LMP1 to achieve functional inhibition of this oncoprotein in EBV-transformed B lymphocytes. We demonstrated that intracellular expression of an endoplasmic reticulum (ER)-targeted form of this sFv markedly reduced LMP1 protein levels. We also observed a decrease in intracellular level of this protein which correlated with a marked reduction of Bcl-2 expression in EBV-transformed B lymphocytes. We further demonstrated that anti-LMP1 sFv-mediated reduction of Bcl-2 correlated with increased sensitivity of these cells to drug-induced cell death. Therefore, these data suggest that an anti-LMP1 sFv used in combination with conventional chemotherapy may be useful for gene therapy of EBV-associated lymphomas in immunocompromised patients.

Original languageEnglish (US)
Pages (from-to)1171-1179
Number of pages9
JournalGene Therapy
Volume5
Issue number9
DOIs
Publication statusPublished - Jan 1 1998

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Keywords

  • Cancer gene therapy
  • EBV
  • Latent membrane protein 1
  • Lymphoproliferative diseases
  • Single-chain antibody

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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