FREQUENT MUTATION IN PX REGION OF HTLV-1 IS OBSERVED IN HAM/TSP PATIENTS, BUT IS NOT SPECIFICALLY ASSOCIATED WITH THE CENTRAL-NERVOUS-SYSTEM LESIONS

Human T-cell leukemia virus type 1 (HTLV-1) is an etiologic agent of adult T-cell leukemia (ATL) and of HTLV-l-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Recently it has been reported that defective HTLV-1 provirus was detected frequently in the central nervous system (CNS) lesions of HAM/TSP patients. Here we investigated sequence variations of the pX region of HTLV-1 in the CNS and peripheral blood lymphocytes (PBL) of the same patient. The results analyzing 9-13 clones isolated from each specimen indicated that the pX region is highly variable within a patient with HAM/TSP, and the mutations were found at almost random positions within the sequences analyzed. The frequency and pattern of those mutations did not appear to differ significantly between the CNS and PBL of the same patient, although they differed among patients. Similarly, frequent mutations were observed in an asymptomatic carrier of HTLV-1, although the variability was moderate, suggesting that the high variability of the pX sequence is not a specific event in HAM/TSP. However, one asymptomatic carrier showed much less frequent variations very similarly to an ATL patient; both of them harbored clonally expanded infected cells. Thus the apparent low variability was explained by clonal selection of a single species of the provirus by the clonal proliferation of infected cells. These results clearly indicate that mutations including defectives are not specifically associated with the CNS lesions in HAM/TSP patients, but suggest that the random mutations simply reflect the rate of viral replication in individuals and the variants were not inherited frequently.