Seroepidemilogic data as well as molecular analysis firmly establishes the association between the human retrovirus human T cell leukemia virus I (HTLV-I) and the diseases adult T cell leukemia/lymphoma (ATL) and tropical spastic paraperesis/HTLV-associated myelopathy (TSP/HAM). However, only a small percentage of those infected with HTLV-I will develop any disease. Because of the inability to detect virus expression by standard ribonucleic acid (RNA) and protein analyses in patients with these diseases, the exact role the virus plays in disease pathogenesis remains unclear. Previously we reported the existence of three new cDNAs capable of coding for new viral proteins using the very sensitive technique, reverse transcriptase-polymerase chain reaction amplification. These messages were detected in RNA from peripheral blood lymphocytes of HTLV-I-infected patients with ATL as well as from infected patients that were asymptomatic. RNase protection analysis of the same infected cell RNA, using specific RNA probes from the newly mapped spliced junctions, confirmed the existence of these alternatively spliced messages and allowed quantitation of them. Genomic and envelope RNA are more abundant than pX mRNA which is more abundant than the alternative singly and doubly spliced pX messages. Previously we reported that recombinant Tax protein (the major transactivating protein of HTLV-I) prepared from an E. coli expression system could be taken up by noninfected lymphocytes and resulted in increased proliferation of cells of lymphoid and glial origin, cell types pertinent to ATL and TSP/HAM, respectively. The protein also enhances the proliferation of T cell colonies from the circulating peripheral blood cells of normal healthy donors supporting the T cell as a direct target for the proliferative effects of Tax. This is pertinent in light of the observation that in ATL, the proliferating cell is a CD4+ T cell. These observations, suggest that Tax protein could exert its effects on uninfected or infected nonexpressing cells in vivo. A strategy aimed at interfering with this protein might be a means of therapy.
