1. ¹UCD Centre for Research in Infectious Diseases, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland
2. ²Department of Neurology, Itoh Hospital, Higashikata, Ibusuki City, Kagoshima, Japan
3. ³Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan

Correspondence: Dr N Sheehy, UCD Centre for Research in Infectious Diseases, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland D4, Ireland. E-mail: Noreen.sheehy@ucd.ie

⁴These authors contributed equally to this work.

Received 15 December 2008; Revised 1 June 2009; Accepted 7 July 2009; Published online 24 August 2009.

Abstract

The Tax protein encoded by human T-cell leukaemia virus type 1 (HTLV-1) has a pivotal role in T-cell transformation by deregulating cellular signalling pathways. Using the yeast two-hybrid system to screen a human leukocyte cDNA library, we identified BCL6 (B-cell lymphoma 6) as a cellular protein, which interacts with Tax 1. The BCL6 gene encodes a sequence-specific transcriptional repressor that contains a conserved N-terminal poxvirus and zinc finger (POZ) repressor domain and a C-terminal Kruppel-like zinc finger DNA binding domain. Using both in vivo and in vitro methods, we demonstrate that the POZ domain of BCL6 is sufficient for its interaction with Tax 1. Using functional assays, we demonstrate that Tax 1 enhanced the repressive activity of BCL6 and increased the levels of apoptosis induced by BCL6 in osteosarcoma cells indicating that both proteins cooperate in vivo to cause a physiological affect. Furthermore, BCL6 recruited Tax 1 into punctate nuclear structures, which suggests that Tax 1 colocalizes with BCL6 in repressor complexes in vivo. BCL6 expression significantly downregulated both basal and Tax-induced nuclear factor-B and long terminal repeat activation. This suggests that the expression of BCL6 in HTLV infected cells may contribute to the silencing of viral gene expression and to the long clinical latency associated with HTLV infection.