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Complete sequence conservation of the human T cell leukaemia virus type 1 tax gene within a family cluster showing different pathologies

Marian E. Major^1,

Ulrich Desselberger^1,,,

¹ Regional Virus Laboratory, East Birmingham Hospital, Birmingham B9 5ST U.K.
and² Midland Centre for Neurosurgery and Neurology, Birmingham B67 7JX, U.K.

We have amplified, through PCR, the full-length tax gene of human T cell leukaemia virus type 1 (HTLV-1) derived from proviral DNA of peripheral blood lymphocytes of five first degree relatives of Afro-Caribbean origin. One patient (the father) had adult T cell leukaemia (ATL), one (the mother) tropical spastic paraparesis (TSP), and three (children) were healthy asymptomatic carriers. All five family members had identical 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, and found to have one and seven nucleotide differences, respectively. At 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 conservation of an HTLV-1 gene following, presumably, horizontal and vertical transmission of the virus. Clones of this gene showed more sequence variation within the TSP patient than the ATL patient, mostly consisting of point mutations; there was no conservation of mutations between 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 lymphocyte response was observed in two asymptomatic carriers with low antibody titres, whereas none was detected in an individual with a high antibody level. No tax-specific sequence was identified which may have contributed to the apparently high degree of transmission from mother to children (three of five children tested) nor account for the differences between disease symptoms in the parents.

Present address: Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, U.K.

Present address: Clinical Microbiology and Public Health Laboratory, Addenbrooke's Hospital, Cambridge CB2 2QW, U.K.

Received 13 May 1993; accepted 25 June 1993.