Adult T-cell leukemia (ATL) is a leukemia derived from mature CD4+ T cells and induced by human T-cell leukemia virus type 1 (HTLV-1) infection. Previous studies have revealed many possible molecular and cellular mechanisms of HTLV-1-induced leukemogenesis, but it still remains unknown how HTLV-1 transforms peripheral CD4 T cells in infected individuals. Given the fact that only 2–5% of infected individuals develop ATL, HTLV-1 infection alone is not sufficient for the transformation of infected cells. Host genetic and epigenetic abnormalities and host immunological status should be considered in attempting to understand the mechanism of the oncogenesis of ATL. Nonetheless, it is obvious that HTLV-1 infection dramatically increases the risk of leukemia generation from peripheral CD4 T-cells, in which the incidence of leukemia is quite low. Furthermore, the evidence that all ATL cases retain the HTLV-1 provirus, especially the region, indicates that HTLV-1-encoded genes play a critical role in leukemogenesis. Since increasing evidence indicates that the HTLV-1 bZIP factor (HBZ) gene plays a significant role in the pathogenesis of HTLV-1, we will discuss the cellular and molecular mechanism of ATL generation from the virological point of view, particularly focusing on HBZ. 1. Introduction Human T-cell leukemia virus type 1 (HTLV-1) is a complex retrovirus that infects approximately 10 to 20 million people worldwide [1]. In the late 1970s, adult T-cell leukemia (ATL) was identified as a distinct clinical entity based on its clinical and geographical features, suggesting an association with unknown infectious agents [2]. Thereafter, HTLV-1 was identified in a cell line derived from a patient with cutaneous T-cell leukemia in 1980 [3]. HTLV-1 has been shown to immortalize human T-lymphocytes in vitro [4]. In addition, HTLV-1 infection also induces chronic inflammatory diseases, such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) [5, 6], HTLV-1-associated uveitis [7], and HTLV-1-associated lung diseases [8]. The entire HTLV-1 sequence was determined [9] and various approaches were used to elucidate the pathogenesis of the virus. However, over 30 years after the discovery of HTLV-I, it is still not fully understood how HTLV-1 transforms mature CD4 T cells. Recent studies have provided emerging evidence of the significance of HBZ in HTLV-1 pathogenesis. In this review, we discuss the present understanding of HTLV-I infection from the virological aspect particularly via focusing on the role of the HBZ gene. 2. The Strategy of Replication
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