Cytotoxic T lymphocytes and viral mutations in HTLV-I-associated myelopathy

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Patients with HTLV-I-associated myelopathy(HAM)have high proviral load despite vigorous cytotoxic T lymphocytes(CTL)responses to the virus.To elucidate whether HTLV-I-speciflc CTL eliminate HTLV-I in vivo in patients with HAM and whether a mutant virus emerges and predominates during the time course in the patients, we performed a longitudinal analysis of HTLV-I proviral load, frequency and degeneracy of HTLV-I Tax specific CTL, viral sequence, and frequency of mutant virus-specific CTL in three patients with HAM.Frequency and degeneracy of CTL paralleled with the proviral load in the patients.Positive pressures were detected in 3 out of 6 sequences associated with the known CTL epitopes by analyzing synonymous and non-synonymous substitutions of viral sequences.The rate of naturally occurring mutant virus ranged from 0 to 20% in each patient, however, no mutant virus accumulated during the time course even if the virus was not recognized by the CTL. These data suggest that CTL in fact eliminate HTLV-J in vivo and that no escape variant of HTLV-I predominates during the time course.This implies that these CTL epitopes can be targets for vaccine development.