Transduction of dominant negative ATF-1 suppresses the pX gene expression in joint fibroblastic cells derived from HTLV-I transgenic rats

Exp Mol Pathol. 2003 Jun;74(3):309-13. doi: 10.1016/s0014-4800(02)00019-9.

Abstract

Tax (p40Tax) encoded by the env-pX gene of human T-cell leukemia virus type I (HTLV-I) interacts with cyclic adenosine-3',5'-monophosphate response element binding protein/activation transcription factor 1 (CREB/ATF-1) transcription factors of host cells and activates the viral long terminal repeat (LTR) promoter. This molecular interaction induces augmentation of viral gene expression and may result in development of HTLV-I-associated diseases, including adult T-cell leukemia, HTLV-I associated myelopathy/tropical spastic paraparesis, and HTLV-I uveitis. To inhibit this pathway, a dominant negative molecule of ATF-1, ATF-1DN, was used. We transduced ATF-1DN into joint fibroblastic cells derived from transgenic rats carrying the LTR-env-pX-LTR gene of HTLV-I, using the Sindbis virus-based vectors. Expression of the pX gene in cells transduced with ATF-1DN was lower than that in cells with control transfection. A possible application of ATF-1DN to suppress viral gene expression in HTLV-I infected cells can be considered.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 1
  • Animals
  • Animals, Genetically Modified
  • Cells, Cultured
  • Cricetinae
  • DNA-Binding Proteins*
  • Fibroblasts / metabolism
  • Gene Expression Regulation, Viral*
  • Genes, Dominant
  • Genes, pX*
  • Hindlimb
  • Human T-lymphotropic virus 1 / genetics*
  • Rats
  • Retroviridae Proteins, Oncogenic / genetics
  • Retroviridae Proteins, Oncogenic / metabolism
  • Transcription Factors / genetics*
  • Transduction, Genetic*
  • Transfection
  • Viral Regulatory and Accessory Proteins

Substances

  • Activating Transcription Factor 1
  • DNA-Binding Proteins
  • Retroviridae Proteins, Oncogenic
  • Transcription Factors
  • Viral Regulatory and Accessory Proteins
  • pX protein, Human T-lymphotropic virus 1