Genomes of evolutionarily divergent members of the human T-cell leukemia virus family (HTLV-I and HTLV-II) are highly conserved, especially in pX.

Abstract

Human T-cell leukemia virus (HTLV) is a family of related human T-lymphotropic retroviruses closely linked with certain human T-cell malignancies and associated with many cases of acquired immunodeficiency syndrome (AIDS). We isolated and molecularly cloned HTLV from patients with both types of clinical disorders and found by restriction endonuclease mapping and core and envelope protein analysis that at least two evolutionarily divergent viral subgroups exist, HTLV-I and HTLV-II. Previous studies have failed to detect significant nucleotide sequence homology between HTLV-I and HTLV-II even though these different members of the HTLV family share certain biologic properties such as T-cell tropism and transformation. To further test these viruses for conserved regions in their genomes, we examined hybridization between HTLV-I and HTLV-II by using Southern blotting and heteroduplex mapping at different melting points. These two techniques produced similar results, showing that HTLV-I and HTLV-II proviruses have, in fact, strongly conserved nucleotide sequences in the pX region and lesser although still substantial homology in the LTR, gag, pol, and env regions. These data provide experimental evidence that HTLV-II, like HTLV-I, contains pX sequences. Although the function of pX is unknown, its conservation in evolutionarily divergent human T-lymphotropic viruses implies a biologically important function. It is possible, but unproven, that pX could encode proteins involved in T-cell tropism, cell transformation, immune suppression, or other biologic actions characteristic of the HTLV family.

Viral Aetiology of Adult T-Cell Leukaemia

“…The nucleotide sequence homology of the two viruses has been investigated. Studies carried out with Southern blotting and heteroduplex mapping at different melting points showed that both viruses had strongly conserved nucleotide sequences in the pX region and less-conserved regions in the LTR, gag, pol and env regions although they are still substantially homologous (Shaw et al, 1984). These data show that both viruses are evolutionarily divergent members of HTLV and suggest that thepX region of HTLV may play an important role in the transformation of cells.…”

Infection of Rats with Bovine Leukaemia Virus: Establishment of a Virus-producing Rat Cell Line

“…The virus is also of interest because it can serve as an experimental model for a family of lymphotropic retroviruses which contains human T cell leukaemia viruses HTLV-I and HTLV-II (Oroszlan et al, 1982;Shaw et al, 1984). The susceptibility of cells from various animal species to BLV infection in vitro is quite broad (Graves & Ferrer, 1976;Altaner et al, 1987a, b).…”

Critical Role of Human T-Lymphotropic Virus Type 1 Accessory Proteins in Viral Replication and Pathogenesis

“…Interestingly, analogous gene regions encoding the accessory proteins, especially the pX ORF I-encoded p12 I , are highly conserved in the closely related virus HTLV-2 and the nonhuman primate counterpart of HTLV-1, simian T-cell lymphotropic virus type 1 (23,110,115). Further illustration of the conserved nature of these gene regions comes from studies of another member of the deltaretroviruses, bovine leukemia virus (BLV).…”