TAX MUTATION ASSOCIATED WITH TROPICAL SPASTIC PARAPARESIS HUMAN T-CELL LEUKEMIA-VIRUS TYPE I-ASSOCIATED MYELOPATHY

Tumaco, Colombia, is an area with elevated rates of tropical spastic p araparesis/human T-cell leukemia virus type I (HTLV-I)-associated myel opathy (TSP/HAM). We have identified a mutation in nucleotide 7959 of the tax gene of 14 Tumaco HTLV-I isolates (14 positive of 14 tested) t hat was present in 5 of 14 (35%) TSP/HAM patients from Japan and in 8 of 11 (72%) TSP/HAM patients from other geographic locations. In contr ast, this mutation was found in only 2 of 21 (9.5%) HTLV-I-infected su bjects outside of Tumaco who did not have TSP/HAM. tax clones with nuc leotide mutations including one at nucleotide 7959 showed a greater ab ility to transactivate the HTLV-I U3 promoter. However, this effect wa s not observed when two clones that differed only in nucleotide 7959 w ere compared. These results suggest that HTLV-I-infected individuals c arrying isolates with this tar mutation are at higher risk for develop ing TSP/HAM.