Current Perspectives in Human T-Cell Leukemia Virus Type 1 Infection and Its Associated Diseases

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) is a replication-competent human retrovirus associated with two distinct types of diseases: a malignancy of mature CD4⁺ T cells called adult T-cell leukemia-lymphoma (ATL) and a chronic inflammatory central nervous system disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It was the first human retrovirus ever associated with a human cancer. Although most HTLV-1-infected individuals remain asymptomatic for life, a subpopulation develops ATL or HAM/TSP. Although the factors that cause these different manifestations of HTLV-1 infection are not fully understood, accumulating evidence suggests that the complex virus-host interactions, as well as the host immune response against HTLV-1 infection, appear to regulate the development of HTLV-1-associated diseases. This review outlines and discusses the current understanding, ongoing developments, and future perspectives of HTLV-1 research.

Keywords: ATL; HAM/TSP; HBZ; HTLV-1; tax.

FIGURE 1

Genome structure of the HTLV-1 provirus. The proviral DNA with the LTRs and viral transcripts encoded in either the plus or minus strand of the viral genome. Alternative splicing yields doubly spliced (tax, rex and p30), singly spliced (env, p21, p13, and p12) mRNAs as well as the unspliced gag and pol transcript. The structural genes (gag, pol and env) and the pX region are flanked by the 5′ and 3′ LTRs. HBZ, encoded on the minus strand, is transcribed from the 3′ LTR.

FIGURE 2

Role of Tax and HBZ. Two viral genes, Tax and HTLV-1 bZIP factor (HBZ) play critical roles in viral transcription and promotion of T-cell proliferation by interacting cellular factors, which is closely related to the long-term survival and persistence of HTLV-1 in infected individuals and development of HTLV-1-associated diseases. SRF, serum response factor.

FIGURE 3

Roles of HTLV-1 Tax and HBZ in the pathogenesis of ATL and HAM/TSP. This figure illustrates the model for ATL and HAM/TSP development. Both Tax and HBZ play crucial roles in oncogenic and inflammatory processes through multiple mechanisms.