Transduction of dominant negative ATF-1 suppresses the pX gene expression in joint fibroblastic cells derived from HTLV-I transgenic rats.
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.
Ishizu
Akihiro
A
Department of Pathology/Pathophysiology, Division of Pathophysiological Science, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Tsuji
Takahiro
T
Abe
Asami
A
Saito
Saori
S
Takahashi
Toshiyuki
T
Ikeda
Hitoshi
H
Meruelo
Daniel
D
Yoshiki
Takashi
T
D051697:Activating Transcription Factor 1; D000818:Animals; D030801:Animals, Genetically Modified; D002478:Cells, Cultured; D006224:Cricetinae; D004268:DNA-Binding Proteins; D005347:Fibroblasts / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D005799:Genes, Dominant; D016355:Genes, pX; D006614:Hindlimb; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D051381:Rats; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D014161:Transduction, Genetic; D014162:Transfection; D054334:Viral Regulatory and Accessory Proteins
D051697:Activating Transcription Factor 1; D004268:DNA-Binding Proteins; D015682:Retroviridae Proteins, Oncogenic; D014157:Transcription Factors; D054334:Viral Regulatory and Accessory Proteins; C072343:pX protein, Human T-lymphotropic virus 1