Virus inactivation in a proportion of human T-cell leukaemia virus type I-infected T-cell clones arises through naturally occurring mutations

Human T-cell leukaemia virus type I (HTLV-I) is the aetiological agent of a dult T-cell leukaemia/ lymphoma and tropical spastic paraparesis/HTLV-I-ass ociated myelopathy (TSP/HAM). The transactivating protein (Tax) of HTLV-I i s strongly implicated in cellular proliferation. We examined the tax gene a nd 5' long terminal repeat (LTR) sequences in eight naturally infected T-ce ll clones derived from TSP/HAM-affected individuals who were either product ively (proliferate spontaneously) or silently (do not proliferate spontaneo usly) infected. In two silently infected clones point mutations within the proviruses resulted in truncation of the Tax protein. One clone harboured b oth a deleterious tax gene mutation and a point mutation in an enhancer ele ment of the 5' LTR. Sequence changes, immunological escape mutation, integr ation site context and host cell phenotype may ail contribute to the high p roportion of latently or silently infected T-cells found in vivo in virus c arriers.