Molecular biology and pathogenesis of the human T‐cell leukaemia/lymphotropic virus Type‐1 (HTLV‐1)

Abstract

Retroviruses are associated with a variety of diseases, including immunological and neurological disorders, and various forms of cancer. In humans, the Human T-cell Leukaemia/Lymphotropic virus type 1 (HTLV-1), which belongs to the Oncovirus family, is the aetiological agent of two diverse diseases: Adult T-cell leukaemia/lymphoma (ATLL) (Poiesz et al. 1980; Hinuma et al. 1981; Yoshida et al. 1982), as well as the neurological disorder tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM) (Gessain et al. 1985; Rodgers-Johnson et al. 1985; Osame et al. 1986). HTLV-1 is the only human retrovirus known to be the aetiological agent of cancer. A genetically related virus, HTLV-2, has been identified and isolated (Kalyanaraman et al. 1982). However, there has been no demonstration of a definitive aetiological role for HTLV-2 in human disease to date. Simian T-cell lymphotropic viruses types 1 and 2 (STLV-1 and -2) and bovine leukaemia virus (BLV) have also been classified in same group, Oncoviridae, based upon their similarities in genetic sequence and structure to HTLV-1 and -2 (Burny et al. 1988; Dekaban et al. 1995; Slattery et al. 1999). This article will focus on HTLV-1, reviewing its discovery, molecular biology, and its role in disease pathogenesis.

Cellular Transformation by the HTLV-I Tax Protein, a Jack-of-All-Trades

“…The retrovirus human T-cell leukemia virus type I (HTLV-I) (reviewed in Johnson et al, 2001) is associated with two fatal human diseases, adult T-cell leukemia (ATL) (reviewed in Uchiyama, 1997;Bazarbachi and Hermine, 2001), a clonal malignancy of infected mature CD4 þ helper T cells (Poiesz et al, 1980;Yoshida et al, 1982;Yamada, 1983;Kikuchi et al, 1986), and tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM), a neurodegenerative disease (Gessain et al, 1985). Infection with HTLV-I is endemic in parts of Japan, South America, Africa, and the Caribbean (Hinuma et al, 1981Blattner et al, 1982;Saxinger et al, 1984;Slattery et al, 1999).…”

Hematopoietic SCT for adult T-cell leukemia/lymphoma: a review

“…6 There are roughly [15][16][17][18][19][20] million people infected with HTLV-1 worldwide, and the common modalities of transmission are sexually, vertically (mother-child), breast feeding or parenteral (for example, injection drug use and blood transfusion). 3,[7][8][9] In the United States and Europe, the seroprevalence of HTLV-1 is o1%, but increases up to 20% in injection drug users. 2,10 The lifetime risk of developing ATLL in individuals infected with HTLV-1 before the age of 20 is 5%.…”

“…2,10 The lifetime risk of developing ATLL in individuals infected with HTLV-1 before the age of 20 is 5%. 3,6,9 There seems to be a genetic susceptibility to developing ATLL. HLA alleles A26, B4002, B4006 and B4801 predispose to the development of ATLL.…”

Human T-cell leukemia virus type 1 Tax interacts with Chk1 and attenuates DNA-damage induced G2 arrest mediated by Chk1

“…The human T-cell lymphotropic virus type-I (HTLV-I) is the etiologic agent of an aggressive and fatal disease, adult T-cell leukemia (Poiesz et al, 1980;Johnson et al, 2001). The principal target cells for HTLV-I infection in the lymphoid system are mature CD4 þ CD45RO þ T lymphocytes.…”