HTLV-1 oncogenesis (schematic). During chronic infection, HTLV-1 replicates persistently via the turnover of existing HTLV-1–infected T-cell clones and a low rate of infection of new clones. Each infected cell expresses HBZ ∼50% of the time and the plus-strand genes (notably tax) in rare intermittent bursts. The host immune response, particularly the CTL response, reaches an equilibrium with the persistent replication of HTLV-1 at the set point of PVL. The efficacy of the immune response is diminished as ATL develops; Tregs induced or maintained by HBZ may contribute to the immune suppression. The main source of oncogenic mutations appears to be a mitotic replication error. In addition, Tax protein may exert direct oncogenic effects (see “Oncogenic actions of HTLV-1 products”); genome-wide deposition of the transcriptionally repressive mark H3K27me3 also often contributes to ATL oncogenesis. † indicates that in ∼40% of cases of ATL, Tax expression is lost, probably as a result of immune-mediated selection.