HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I (HTLV-I) MOLECULAR GENOTYPES AND DISEASE OUTCOME

The approach taken in our laboratory to determine viral markers associ ated with human T cell leukemia virus type I (HTLV-I) disease inductio n was to compare viral genomes and host immune responses from HTLV-I-i nfected patients from two geographical areas with significant differen ces in the incidence rare of tropical spastic paraparesis/HTLV-I-assoc iated myelopathy (TSP/HAM), Tumaco, Colombia, and Kyushu Island, Japan . These studies showed that TSP/HAM patients have higher antibody leve ls against viral antigens and a higher proviral load compared to asymp tomatic carriers and adult T cell leukemia (ATL) patients. A mutation in the tax gene was found to be associated with TSP/HAM, which in turn correlates with a higher transactivation activity of Tax. In addition , we found that HTLV-I-infected individuals contain infected cells tha t are clonally expanded. The genomic structure of these expanded clone s shows that defective proviruses are present in asymptomatic carriers . A predilection in the defectiveness, however, was found to correlate with the presence (Cosmopolitan molecular genotype) or absence of the tax mutation (Japanese molecular genotype), Our results suggest that defective proviruses retaining structural genes might be a risk factor for TSP/HAM development, Contrary, defective proviruses retaining reg ulatory genes in the pX region could be a risk factor for ATL developm ent, The molecular mechanism by which these defective proviruses is ge nerated and expressed should give new insight into HTLV-I pathogenesis .