{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The HTLV‐1 basic leucine zipper (HBZ) factor is a multifunctional viral protein that plays pivotal roles in viral latency, cell proliferation, and oncogenesis. HBZ is expressed constitutively from the antisense strand of the HTLV‐1 provirus, and its activities are mediated through diverse interactions with cellular transcription factors and coactivators. On one hand, HBZ represses viral gene transcription by dimerizing with members of the ATF/CREB family and competing for binding to key coactivators such as p300/CBP, thereby counteracting the actions of the potent viral transactivator Tax (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " On the other hand, HBZ modulates the activity of several cellular signaling pathways. For example, it selectively suppresses the classical NF‑κB pathway by binding to the p65 subunit and promoting its degradation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", and it differentially interacts with AP‑1 family members – repressing c‐Jun/JunB activity while activating JunD‐dependent transcription."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Through its cooperation with JunD and recruitment of Sp1, HBZ can also upregulate the transcription of genes such as the human telomerase catalytic subunit (hTERT), thereby enhancing telomerase activity and contributing to immortalization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Furthermore, by modulating NF‑κB and antagonizing Tax‐induced senescence"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", as well as by interacting with factors like ATF3"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", HBZ creates a cellular milieu that favors continued proliferation and survival of infected T cells. Additional studies have revealed that HBZ can enhance its own transcription in a feedback loop involving JunD and Sp1"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", modulate immune regulatory cytokines such as IL‑10, and even influence cytoplasmic signaling pathways including mTOR through interactions with proteins like GADD34."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Finally, by attenuating tumor suppressor functions—for instance, by repressing p53 activity via interference with histone acetyltransferases"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "and by influencing anti‐apoptotic gene expression"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "—HBZ contributes to the persistence and oncogenic potential of HTLV‑1–infected cells. Collectively, these studies underscore the dual role of HBZ as both a repressor of viral transcription and a modulator of cellular pathways that together promote viral persistence, immune evasion, and leukemogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)\n <br />\n <small>\n 1"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "&nbsp;|&nbsp;\n 2"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "&nbsp;|&nbsp;\n 3"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "&nbsp;|&nbsp;\n 4"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "&nbsp;|&nbsp;\n 5"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "&nbsp;|&nbsp;\n 6"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "&nbsp;|&nbsp;\n 7"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "&nbsp;|&nbsp;\n 8"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "&nbsp;|&nbsp;\n 9"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "&nbsp;|&nbsp;\n 10"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "&nbsp;|&nbsp;\n 11"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "&nbsp;|&nbsp;\n 12"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "</small>\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Isabelle Clerc, Nicholas Polakowski, Charlotte André-Arpin, et al. 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