COMPLETE SEQUENCE CONSERVATION OF THE HUMAN T-CELL LEUKEMIA-VIRUS TYPE-1 TAX GENE WITHIN A FAMILY CLUSTER SHOWING DIFFERENT PATHOLOGIES

We have amplified, through PCR, the full-length tax gene of human T ce ll leukaemia virus type 1 (HTLV-1) derived from proviral DNA of periph eral blood lymphocytes of five first degree relatives of Afro-Caribbea n origin. One patient (the father) had adult T cell leukaemia (ATL), o ne (the mother) tropical spastic paraparesis (TSP), and three (childre n) were healthy asymptomatic carriers. All five family members had ide ntical tax nucleotide sequences as determined by direct sequencing of PCR products. This sequence was compared with tax gene sequences of an unrelated TSP patient of Afro-Caribbean origin, and of C8166 cells, a nd found to have one and seven nucleotide differences, respectively. A t the amino acid level these three sequences differed from the HTLV-1 prototype Japanese strain (ATK-1). All sequence changes were clustered towards the 3' end of the gene. These data demonstrate the complete c onservation of an HTLV-1 gene following, presumably, horizontal and ve rtical transmission of the virus. Clones of this gene showed more sequ ence variation within the TSP patient than the ATL patient. mostly con sisting of point mutations; there was no conservation of mutations bet ween the two individuals. These mutations occurred only in individual clones of the ATL patient whereas those of the TSP patient were found to be repeated in different clones. A tax-specific cytotoxic T lymphoc yte response was observed in two asymptomatic carriers with low antibo dy titres, whereas none was detected in an individual with a high anti body level. No tax-specific sequence was identified which may have con tributed to the apparently high degree of transmission from mother to children (three of five children tested) nor account for the differenc es between disease symptoms in the parents.