| Summary: | Human T-cell leukemia virus type 1 (HTLV-1) establishes persistent infection in vivo in two distinct ways: de novo infection and clonal proliferation of infected cells. Two viral genes, Tax and HTLV-1 bZIP factor (HBZ) play critical roles in viral transcription and promotion of T-cell proliferation, respectively. Tax is a potent transactivator not only for viral transcription but also for many cellular oncogenic pathways, such as the NF-κB pathway. HBZ is a suppressor of viral transcription and has the potential to change the immunophenotype of infected cells, conferring an effector regulatory T cell (eTreg)-like signature (CD4+ CD25+ CCR4+ TIGIT+ Foxp3+) and enhancing the proliferation of this subset. Reports that mice transgenic for either gene develop malignant tumors suggest that both Tax and HBZ are involved in leukemogenesis by HTLV-1. However, the immunogenicity of Tax is very high, and its expression is generally suppressed in vivo. Recently, it was found that Tax can be expressed transiently in a small subpopulation of adult T-cell leukemia-lymphoma (ATL) cells and plays a critical role in maintenance of the overall population. HBZ is expressed in almost all infected cells except for the rare Tax-expressing cells, and activates the pathways associated with cell proliferation. These findings indicate that HTLV-1 fine-tunes the expression of viral genes to control the mode of viral propagation. The interplay between Tax and HBZ is the basis of a sophisticated strategy to evade host immune surveillance and increase transmission – and can lead to ATL as a byproduct.
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