Abstract
Human T cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus responsible for the development of adult T-cell leukemia (ATL). Although HTLV-1 harbors an oncogene, tax, that transforms T cells in vitro and induces leukemia in transgenic mice, tax expression is frequently disrupted in ATL, making the oncogenesis of ATL a bit mysterious. The HTLV-1 bZIP factor (HBZ) gene was discovered in 2002 and has been found to promote T-cell proliferation and cause lymphoma in transgenic mice. Thus HBZ has become a novel hotspot of HTLV-1 research. This review summarizes the current findings on HBZ with a special focus on its potential links to the oncogenesis of ATL. We propose viewing HBZ as a critical contributing factor in ATL development.
Highlights
Human T-cell leukemia virus type 1 (HTLV-1) is the first human retrovirus to have been identified, and it was later demonstrated to be the causative agent of adult T-cell leukemia (ATL), an aggressive cancer of peripheral CD4 T cells [1, 2]
HTLV-1 is able to infect various cell types in vitro, yet the HTLV-1 provirus is predominantly detected in CD4 T cells in vivo [3]
The HTLV-1 provirus is 9 kb long and has multiple coding regions flanked by two identical 750-bp long terminal repeats (LTRs) in the 5′ and 3′ ends (Fig. 1), both of which are composed of unique 3′ (U3), repeat (R) and unique 5′ (U5) regions
Summary
Human T-cell leukemia virus type 1 (HTLV-1) is the first human retrovirus to have been identified (in the early 1980s), and it was later demonstrated to be the causative agent of adult T-cell leukemia (ATL), an aggressive cancer of peripheral CD4 T cells [1, 2]. HTLV-1 is able to infect various cell types in vitro, yet the HTLV-1 provirus is predominantly detected in CD4 T cells in vivo [3]. The CD4 T cell tropism of HTLV-1 is likely due to selected expansion of infected CD4 T cells rather than a receptor preference, because the HTLV-1 receptor, glucose transporter 1 (GLUT1) is ubiquitously expressed [4, 5]. The HBZ gene Tax is of crucial importance for its unique ability to drive HTLV-1 replication and to immortalize T cells [12] and has long been thought to be the main causal factor of ATL. It has been reported that Tax expression is frequently inactivated in ATL cases by either abortive mutations in the tax gene or DNA methylation of the 5′ LTR [13,14,15,16]. Host immunosurveillance by cytotoxic T lymphocytes (CTLs) is thought to
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