HTLV-1

In recent years, the human T-cell leukemia virus, type 1 (HTLV-1) has become increasingly recognized as an important cause for public health concern throughout the world. 

Facts about HTLV-1:

 Discovered in 1980, associated with an aggressive T-cell leukemia

 The first pathogenic human retrovirus identified

 Transmission is similar to HIV, although HTLV-I is one-tenth as infective

 Generally develops >40 years following infection

 Lytic bone lesions in the skull and long bones

 Skin lesions due to infiltration of leukemic cells

 Unresponsive to aggressive chemotherapy

 Median survival ~6 months

 Fifteen to twenty million people infected worldwide


Review: The neurology of HTLV-1 infection. 
S A CooperM Schim van der LoeffG P Taylor. Pract Neurol 2009;9:1 16-26 doi:10.1136/jnnp.2008.167155.


A large body of evidence suggests that the clinical manifestations of HTLV-1 infection occur as a consequence of a virally-encoded protein called Tax. Our laboratory focuses on defining the intracellular consequences of Tax expression in the infected human cell, with emphasis on the Tax-dependent events that lead to malignant transformation.

Tax Diagram


Tax is critical to the viral life cycle, as it activates HTLV-I transcription. Recent studies demonstrate that the cellular coactivator CBP/p300 associates with Tax to potentiate transcriptional activation of the viral genome.

Promoter

CBP/p300 is a coactivator that regulates transcription through interaction with a wide variety of structurally unrelated transcription factors. CBP/p300 belongs to a novel class of recently described transcriptional coactivators proteins that possess histone acetyltransferase (HAT) activity, and appear to play a role in gene-specific activation through modulation of chromatin structure. Although the precise role of the HAT activity of CBP/p300 is unknown, there is a strong link between abnormalities in acetylase function, aberrant chromatin acetylation, and human cancers. These observations suggest that alterations in expression of CBP/p300 expression and/or function is a common denominator in many human malignancies, especially leukemias.

The strong correlation between CBP/p300 deregulation and human malignancies forms the basis for the premise that the physical interaction between CBP/p300 and Tax plays a causal role in neoplastic transformation of the HTLV-I infected T-cell. Our laboratory is exploring CBP/p300 transcription function using both in vitro and in vivo approaches. Our methods should allow biochemical dissection of the Tax-CBP/p300 interactions that accompany transcriptional activation. The outcome of our research may reveal basic aspects of CBP/p300 and Tax function as they pertain to gene regulation, chromatin structure, and leukemogenesis.


The Nyborg Lab at Colorado State University © 2012