Human T cell leukemia virus types 1 and 2 (HTLV-1 and HTLV-2) are genetically related complex retroviruses that are capable of immortalizing human T-cells in vitro and establish life-long persistent infections in vivo. In spite of these apparent similarities, HTLV-1 and HTLV-2 exhibit a significantly different pathogenic potential. HTLV-1 is recognized as the causative agent of adult T-cell leukemia/lymphoma (ATLL) and tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). In contrast, HTLV-2 has not been causally linked to human malignancy, although it may increase the risk of developing inflammatory neuropathies and infectious diseases. The present paper is focused on the studies aimed at defining the viral genetic determinants of the pathobiology of HTLV-1 and HTLV-2 through a comparison of the expression strategies and functional properties of the different gene products of the two viruses. 1. Introduction Human T-cell leukemia virus types 1 and 2 (HTLV-1 and HTLV-2) are related deltaretroviruses [1] with similar genetic organization [2–7]. The two viruses share an average 65% homology at the nucleotide level, with higher conservation in the gag, pol, env, and tax/rex genes and lower in the long terminal repeats (LTR), protease, and proximal “X region,” a region located at the 3′ end of the genome. Although both viruses immortalize T cells in culture and establish life-long persistent infections in vivo, they exhibit a significantly different pathogenic potential. HTLV-1 is recognized as the causative agent of adult T-cell leukemia/lymphoma (ATLL) and tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). In contrast, HTLV-2 has not been causally linked to human malignancy. However, large cohort studies revealed that HTLV-2 infection may be associated with lymphocytosis, increased risk of developing inflammatory neuropathies, infectious diseases, and with increased all-cause mortality [4–6, 8]. Furthermore, coinfection with HTLV-2 plays an important role in the progression of HIV-infected patients to AIDS [9]. In the present paper, we will focus on the discussion of studies aimed at comparing the expression strategies, regulation, and pathogenic properties of HTLV-1 and HTLV-2. 2. The Genetic Organization and Expression Strategy of HTLV-1 and HTLV-2 Like other complex deltaretroviruses, HTLV-1 and HTLV-2 are characterized by the presence of the “X region,” in addition to the LTR and the gag, pol, and env genes present in all retroviruses. The coding potential of the HTLV genomes is greatly enhanced by several expression
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