Comparison of the Genetic Organization, Expression Strategies and Oncogenic Potential of HTLV-1 and HTLV-2

Abstract

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.

Figure 1

Comparison of the organization, alternative splicing, and coding potential of HTLV-1 and HTLV-2 mRNAs. Exon composition and coding potential of HTLV-1 and HTLV-2 alternatively spliced mRNAs. ORFs are indicated by colored boxes. Splice sites are indicated by numbers. n.d.: not determined.

Figure 2

Schematic representation of Tax-1 and Tax-2 structural and functional domains. The positions of the amino acids modified by ubiquitination, sumoylation, acetylation, and phosphorylation are indicated.

Figure 3

Comparison of the protein isoforms coded by the x-III ORF of HTLV-1 and HTLV-2. Indicated is the exon composition of the mRNAs (left) and the domain structure of the corresponding proteins (right) coded by the x-III ORFs of HTLV-1 and HTLV-2. HTLV-1 produces a single truncated x-III ORF: p21rex; HTLV-2 produces a family of truncated x-III isoforms ranging from 22 to 17 kDa. RBD/NLS: rna binding domain/nuclear localization signal; MD: multimerization domain; AD/NES: activation domain/nuclear export signal; PS: phosphorylation site.

Figure 4

Comparison of the cis acting regulatory elements of HTLV-1 and HTLV-2. Position of the cis acting posttranscriptional regulatory elements of HTLV-1 and HTLV-2 are indicated. RXRE: Rex-responsive element; CRS: cis-acting repressive sequences; CSE: cis-acting stimulatory element; CIE: cis acting inhibitory elements.