PATHOGENIC PROPERTIES OF HTLV-II

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The human T cell leukemia viruses, type 1 (HTLV-I) and type II (HTLV-II) are closely related members of a family of retroviruses which have similar biological properties and a tropism for T lymphocytes. HTLV-1 is associated with both lymphoproliferative and neurological disorders. Although the role of HTLV-II in human disease has yet to be completely understood, recent studies have suggested that infection is also associated with neurological disorders. To better understand the pathogenicity of HTLV-II we have been studying the molecular properties of the virus and the immunological features associated with infection. In preliminary studies we have demonstrated that there are at least two closely related, but distinct molecular subtypes of the virus. In addition, it could be shown, that in contrast to HTLV-I, which has a preferential tropism for CD4+ T lymphocytes, HTLV-II appears to preferentially infect CD8+ T lymphocytes. We intend to expand on these preliminary observations and propose the following studies. First we will carry out extensive nucleotide sequence analysis of selected gene regions of a large number of proviruses. This should allow a more detailed classification of the viruses, and perhaps the identification of additional subtypes. In parallel with this we will initiate studies to determine if the major subtypes may have phenotypic differences. It is also intended to confirm and extend our preliminary observations that the virus has a preferential -tropism for CD8+ T lymphocytes and we will investigate if infection may be associated with clonal expansion of certain CD8 populations. These studies should not only increase our understanding of the pathogenic properties of the virus, but will also provide a strong foundation for studying its role in human disease.