Human T-cell leukaemia virus type 1 (HTLV-1) infectivity and cellular transformation

Abstract

Human T-cell leukaemia virus type 1 (HTLV-1), a retrovirus that infects 20 million people worldwide, was the first retrovirus to be shown to be causal for a human cancer, adult T-cell leukaemia (ATL). The infectivity of HTLV-1 is tightly cell-associated, and is mediated through a virological synapse. Cell-free virus is largely non-infectious. HTLV-1 does not use viral capture of a cellular proto-oncogene for oncogenesis. Its viral oncoprotein, Tax, is needed to initiate but not maintain cellular transformation. Tax transforms cells through various mechanisms, including the creation of chromosomal instability, the amplification of centrosomes, the abrogation of DNA repair, the activation of cyclin-dependant kinases and nuclear factor κB (NFκB) and Akt signalling, and the silencing of p53 and spindle-assembly checkpoints. The maintenance of ATL transformation seems to require the function of a novel antisense protein and RNA, termed HTLV-1 basic leucine zipper factor (HBZ).