HTLV-1 can infect various cell types including B and T lymphocytes, dendritic cells, and synovial cells, suggesting that its receptor is ubiquitously expressed on cell surfaces. However, HTLV-1 is predominately found in CD4+ lymphocytes (Yasunaga et al., 2001) while HTLV-2 infects peripheral blood mononuclear cells, although there have been studies of preferential tropism for CD8+ T cells (Ijichi et al., 1992; Miyamoto et al., 1991; Lal et al., 1993a). HTLV-1/2 entry is mediated through interaction of the surface unit of the virion envelope glycoprotein (SU) with its cellular receptor GLUT1, a glucose transporter, on target cells (Manel et al., 2003). HTLV-1 and HTLV-2 can efficiently immortalize and transform T lymphocytes in vitro and persist in infected individuals or experimental animals. The basis for HTLV-mediated cellular transformation is poorly understood, but clearly involves the viral transactivator protein Tax.
Pathology of HTLV
Schematic model of the natural course from HTLV-1 infection to the onset of ATL.
Adapted from Yasunaga J, Matsuoka M. Leukemogenesis of adult T-cell leukemia.
Int J Hematol. 2003;78:312-320.
Although HTLV-2 is highly related to HTLV-1, infection with HTLV-2 is not linked with development of lymphoproliferative disorders, and is less pathogenic than HTLV-1. It remains unclear why infection with HTLV-1 is more pathogenic in comparison with infection with HTLV-2 but studies have hypothesized that this differential pathogenic potential might be attributable to differences in the respective Tax activities. These differences are likely to provide the basis for the different clinical manifestations of these two viruses.
HTLV-1 transmits naturally in a cell-to-cell fashion; therefore, infected cells are essential for transmission. After infection, HTLV-1 promotes clonal proliferation of infected cells by pleiotropic actions of Tax and other viral proteins such as HBZ. Proliferation of HTLV-1 infected cells is controlled by cytotoxic T cells (CD8+) in vivo. After a long latent period of about 60years, ATLL develops in about 5% asymptomatic carriers (Okamoto et al., 1989). In late phase, the expression of Tax is inactivated by several mechanisms, suggesting that Tax is not necessary at this stage; however, HBZ is important in all phases. Together with accumulated alternations of host genome during the latency period, it finally leads to the onset of ATLL.
Masao Matsuoka. Human T-cell leukemia virus type I and adult T-cell leukemia. Oncogene. 2003;22:5131-5140
Mitsuaki Yoshida. Discovery of HTLV-1, the first human retrovirus, its unique regulatory mechanisms, and insights into pathogenesis. Oncogene. 2005;24:5931-5937
Feuer et. al. Comparative biology of human T-cell .lymphotropic virus type I (HTLV-1) and HTLV-2. Oncogene. 2005;24:5996-6004
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