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 adult T-cell leukaemia/lymphoma and tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). The trans-activating protein (Tax) of HTLV-I is strongly implicated in cellular proliferation. We examined the tax gene and 5' long terminal repeat (LTR) sequences in eight naturally infected T-cell clones derived from TSP/HAM-affected individuals who were either productively (proliferate spontaneously) or silently (do not proliferate spontaneously) infected. In two silently infected clones point mutations within the proviruses resulted in truncation of the Tax protein. One clone harboured both a deleterious tax gene mutation and a point mutation in an enhancer element of the 5' LTR. Sequence changes, immunological escape mutation, integration site context and host cell phenotype may all contribute to the high proportion of latently or silently infected T-cells found in vivo in virus carriers.
Rose
N J
NJ
University of Cambridge Department of Medicine, Level 5, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.
Richardson
J H
JH
Desselberger
U
U
Lever
A M
AM
D020121:5' Untranslated Regions / Q000235:genetics; D000328:Adult; D001483:Base Sequence; D002999:Clone Cells; D004742:Enhancer Elements, Genetic; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism; D016355:Genes, pX; D015490:HTLV-I Infections / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000235:genetics* / Q000254:growth & development* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D017354:Point Mutation; D013601:T-Lymphocytes / Q000821:virology*; D020079:Terminal Repeat Sequences / Q000235:genetics; D014158:Transcription, Genetic; D014775:Virus Activation / Q000502:physiology
D020121:5' Untranslated Regions; D016356:Gene Products, tax