M. Saito et al., 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/, Journal of neurovirology, 1(3-4), 1995, pp. 286-294
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.