The human T-cell leukemia/lymphotropic virus type I (HTLV-I) is the etiologic agent of adult T-cell leukemia/lymphoma (ATL) and tropical spastic paraparesis/ HTLV-I-associated myelopathy (TSP/HAM); however, only a small percentage of those infected with HTLV-I will develop disease. The goal is to further understand viral- and cell-specific factors that might determine disease pathogenesis during HTLV-I infection. The existence of newly recognized alternatively spliced viral messenger ribonucleic acids (mRNA) from the pX region of HTLV-I have been reported. Regulation of the expression of these alternatively spliced messages and/or expression of proteins encoded by these regions may influence the outcome of infection in the host. RNase protection analysis of total RNA from peripheral blood cells from patients with ATL as well as cell lines established from patients with ATL and TSP/HAM using specific RNA probes from the newly mapped spliced junctions confirmed the existence of these alternatively spliced messages and indicated that they could be found during infection established from viral strains of different pathogenic origin and that the relative abundance of each RNA differed from sample to sample, indicating a clear regulatory mechanism at the level of utilization of alternative splice sites. The cell lines have been further characterized for any correlation between specific viral gene expression and interleukin 2 dependence and independence, but no clear relationship was found. Primary peripheral blood cells obtained form patients with ATL also had a detection of specific HTLV-I pX messages by this method. These same samples had a high level expression of myc and variable expression of the protein kinase, LCK. Analysis of the relationship between expression of specific viral mRNA's and oncogenes and tumor suppressor genes known to be involved with tumorigenesis will give us further insight into the role these novel viral genes play in disease pathogenesis.
