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Human T-lymphotropic virus type I: Virology, pathogenesis, and epidemiology

David T Scadden, MD
Andrew R Freedman, FRCP
Paul Robertson, MRCP, FRCPath
Section Editor
Martin S Hirsch, MD
Deputy Editor
Allyson Bloom, MD


Human T-lymphotropic virus (HTLV-I), the first human retrovirus to be discovered [1], is estimated to infect 5 to 10 million people worldwide [2,3]. This virus is the causative agent of two typically fatal diseases: adult T cell leukemia-lymphoma (ATL) [4-6] and HTLV-I-associated myelopathy (HAM) [7], which is also known as tropical spastic paraparesis (TSP) [8].

The epidemiology, virology, and pathogenic features of HTLV-I will be reviewed here. The diagnosis, disease associations, and treatment are discussed separately. (See "Human T-lymphotropic virus type I: Disease associations, diagnosis, and treatment".)


HTLV-I is an enveloped, single-stranded RNA virus of the Retroviridae family, the only human pathogen of the subfamily oncovirus, which includes HTLV-2, bovine leukemia virus (BLV), simian T cell leukemia virus (STLV) and HTLV-3 and HTLV-4 [9]. It has a diploid genome, comprised of two identical strands of positive sense RNA, each 9032 bp long. The genomic organization is similar to other retroviruses, with two long terminal repeat (LTR) sequences flanking gag, pol, and env genes (figure 1).

However, HTLV-I also possesses a unique 1.6 kb region, termed pX, which is located between env and the 3'LTR [10]. This region encodes a number of regulatory proteins: p40tax (Tax), p27rex, p21rex, p12, p13 and p30. HTLV-1 basic leucine zipper factor (HBZ) is encoded by the minus (complementary) strand of pX region [11]. Of these, Tax and HBZ have been most implicated in viral pathogenesis. (See 'Pathogenesis' below.)

Cell entry and replication — HTLV-I displays CD4 T cell tropism, but virion entry to CD4 T cells occurs most efficiently by direct cell-to-cell contact, rather than from virions free in plasma. Cell-free HTLV-1 can also infect dendritic cells (via heparin sulphate proteoglycans and neuropilin-1) [12] and can subsequently be transmitted from dendritic cells to CD4 T cells [13]. The glucose transporter, glut-1 [14,15], has also been identified as a receptor for the HTLV-1 envelope glycoprotein (env). However, cells lacking GLUT-1 expression can be infected by HTLV-1 [16].

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Literature review current through: Nov 2017. | This topic last updated: Jun 21, 2016.
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