Disruption of transcription network of cellular genes by human T-cell leukemia virus type-1.

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Human T-cell leukemia virus type-1 (HTLV-1) infection causes adult T-cell leukemia (ATL). Modulation of the transcriptional control of cellular genes by HTLV-1 is thought to be associated with the development of ATL. The viral protein HTLV-1 basic leucine-zipper factor (HBZ) has been shown to dysregulate the activity of cellular transcription factors. We evidence that HBZ reduced both IRF-1 DNA-binding activity and stability via a proteasome-dependent pathway. In addition, IRF-1-mediated apoptosis is significantly reduced by ectopic production of the HBZ. Also, we demonstrate that HBZ is exported from the nucleus to the cytoplasm, where it activates the mTOR signaling pathway through an association with growth arrest and DNA damage gene 34 (GADD34). Starvation-induced autophagy is significantly suppressed by the overexpression of HBZ.