HTLV-1 p30II: selective repressor of gene expression

Patrick L Green

doi:10.1186/1742-4690-1-40

Abstract

Human T-lymphotropic virus type-1 (HTLV-1) is a complex retrovirus that causes adult T-cell leukemia/lymphoma (ATL) and is implicated in a variety of lymphocyte-mediated disorders. HTLV-1 pX ORF II encodes two proteins, p13II and p30II whose roles are beginning to be defined in the virus life cycle. Previous studies indicate the importance of these viral proteins in the ability of the virus to maintain viral loads and persist in an animal model of HTLV-1 infection. Intriguing new studies indicate that p30II is a multifunctional regulator that differentially modulates CREB and Tax-responsive element-mediated transcription through its interaction with CREB-binding protein (CBP)/p300 and specifically binds and represses tax/rex mRNA nuclear export. A new study characterized the role of p30II in regulation of cellular gene expression using comprehensive human gene arrays. Interestingly, p30II is an overall repressor of cellular gene expression, while selectively favoring the expression of regulatory gene pathways important to T lymphocytes. These new findings suggest that HTLV-1, which is associated with lymphoproliferative diseases, uses p30II to selectively repress cellular and viral gene expression to favor the survival of cellular targets ultimately resulting in leukemogenesis.

Highlights

The complex sequence of events set in motion by human T-lymphotropic virus type 1 (HTLV-1) to cause proliferation and transformation of T lymphocytes is beginning to be unraveled
Recent studies have indicated novel roles for pX open reading frames (ORF) I and II gene products in the replication of HTLV-1 [7,8,9]. The study of these gene products were largely bypassed by virologists until the mid 1990's, they intensified when infectious molecular clones provided the tools to better understand their role in vivo. Both HTLV-1 pX ORF I and II mRNAs have been detected in infected cell lines and blood leukocytes from HTLV-1-infected subjects including adult T-cell leukemia/lymphoma (ATL) and HAM/TSP patients [10,11]
The cell nucleus surrounded by the nuclear membrane and key components are shown. p30II can directly interact with CREB binding protein (CBP)/p300 and modulate transcription of viral and/or cellular genes

Summary

Introduction

The complex sequence of events set in motion by human T-lymphotropic virus type 1 (HTLV-1) to cause proliferation and transformation of T lymphocytes is beginning to be unraveled. Recently has it become clear that viral encoded proteins, the so-called "accessory" gene products of this complex retrovirus, play an integral role in the pathogenic process. In addition to the structural and enzymatic gene products, HTLV-1 encodes regulatory and accessory proteins from four open reading frames (ORF) in the pX region between env and the 3' long terminal repeat (LTR) of the provirus [1,2].

Results

Conclusion