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 a dult T-cell leukemia (ATL) and of HTLV-l-associated myelopathy/tropica l spastic paraparesis (HAM/TSP). Recently it has been reported that de fective HTLV-1 provirus was detected frequently in the central nervous system (CNS) lesions of HAM/TSP patients. Here we investigated sequen ce variations of the pX region of HTLV-1 in the CNS and peripheral blo od lymphocytes (PBL) of the same patient. The results analyzing 9-13 c lones isolated from each specimen indicated that the pX region is high ly variable within a patient with HAM/TSP, and the mutations were foun d at almost random positions within the sequences analyzed. The freque ncy and pattern of those mutations did not appear to differ significan tly between the CNS and PBL of the same patient, although they differe d among patients. Similarly, frequent mutations were observed in an as ymptomatic carrier of HTLV-1, although the variability was moderate, s uggesting that the high variability of the pX sequence is not a specif ic event in HAM/TSP. However, one asymptomatic carrier showed much les s frequent variations very similarly to an ATL patient; both of them h arbored clonally expanded infected cells. Thus the apparent low variab ility was explained by clonal selection of a single species of the pro virus by the clonal proliferation of infected cells. These results cle arly 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.