Human T cell leukemia (HTLV) is a retroviral family associated with a number of human diseases, including adult T cell leukemia/lymphoma, hairy cell leukemia, and acquired immune deficiency syndrome (AIDS). The genome of HTLV possesses a unique region at its 3' end designated pX. The pX region consists of four open reading frames. It is unknown whether this region is expressed during HTLV infection or transformation. We wish to investigate the structure, origin, expression and function of the pX region. The structure of the pX region will be determined by restriction endonuclease mapping, hybridization studies and primary DNA sequence analysis of cloned HTLV isolates. The origin of the pX region will be investigated by Southern blot analysis of vertebrate DNAs under relaxed conditions of hybridization. The expression of the pX region will be studied by Northern blot analysis of HTLV-associated tumors. We plan to use in vitro translation of hybrid-selected RNAs, expression in eukaryotic and bacterial systems, and synthetic peptides to study the protein products of this region. Functional analysis of the pX proteins will be done by characterizing the phenotypic effects of pX expression in eukaryotic cells, by observing the effect of pX deletions on HTLV replication and in vitro immortalization ability and by determining whether the presence of the pX region affects the replication and/or pathogenicity of animal leukemia viruses.
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