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 paraparesis/human T-cell leukemia virus type I (HTLV-I)-associated myelopathy (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) that 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 contrast, this mutation was found in only 2 of 21 (9.5%) HTLV-I-infected subjects outside of Tumaco who did not have TSP/HAM. tax clones with nucleotide mutations including one at nucleotide 7959 showed a greater ability to transactivate the HTLV-I U3 promoter. However, this effect was not observed when two clones that differed only in nucleotide 7959 were compared. These results suggest that HTLV-I-infected individuals carrying isolates with this tax mutation are at higher risk for developing TSP/HAM.
Renjifo
B
B
Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts 02115.
Borrero
I
I
Essex
M
M
D003105:Colombia / Q000453:epidemiology; D004279:DNA, Viral; D016355:Genes, pX; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D009154:Mutation; D015493:Paraparesis, Tropical Spastic / Q000453:epidemiology / Q000821:virology*
D004279:DNA, Viral