Functional analysis of two long terminal repeats from the HTLV-I retrovirus

Abstract

Human T-cell leukemia virus type I (HTLV-I) is associated with a large spectrum of clinical manifestations in man. Viral and host factors are probably involved in determining the consequences of infection. Although most of the genome of HTLV-I appears remarkably stable, considerable variation is observed in the long terminal repeat (LTR) which harbors the promoter region. So far, no correlation between specific mutations and pathogenesis has been found, and the current opinion is that sequence variations reflect the geographical origin of the isolate more than the associated pathology. To assess whether the mutations observed between two HTLV-I LTRs were functionally significant, two LTRs, which differ by ten mutations, were coupled to the highly sensitive eukaryotic luciferase-encoding reporter gene, luc, and tested by transfection in a variety of cell lines. Marked differences in promoter activity were observed in some of the cells tested, whereas in others both LTRs were equally active. This result demonstrates that the minor differences observed between two HTLV-I LTRs can affect the activity level of the promoter in some cellular environments, a result which could point to the LTR as one determinant of HTLV-I cell tropism in vivo.