Of the members of the primate T cell lymphotropic virus (PTLV) family, only the human T-cell leukemia virus type-1 (HTLV-1) causes disease in humans—as the etiological agent of adult T-cell leukemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and other auto-inflammatory disorders. Despite having significant genomic organizational and structural similarities, the closely related human T-cell lymphotropic virus type-2 (HTLV-2) is considered apathogenic and has been linked with benign lymphoproliferation and mild neurological symptoms in certain infected patients. The silencing of proviral gene expression and maintenance of latency are central for the establishment of persistent infections in vivo. The conserved pX sequences of HTLV-1 and HTLV-2 encode several ancillary factors which have been shown to negatively regulate proviral gene expression, while simultaneously activating host cellular proliferative and pro-survival pathways. In particular, the ORF-II proteins, HTLV-1 p30II and HTLV-2 p28II, suppress Tax-dependent transactivation from the viral promoter—whereas p30II also inhibits PU.1-mediated inflammatory-signaling, differentially augments the expression of p53-regulated metabolic/pro-survival genes, and induces lymphoproliferation which could promote mitotic proviral replication. The ubiquitinated form of the HTLV-1 p13II protein localizes to nuclear speckles and interferes with recruitment of the p300 coactivator by the viral transactivator Tax. Further, the antisense-encoded HTLV-1 HBZ and HTLV-2 APH-2 proteins and mRNAs negatively regulate Tax-dependent proviral gene expression and activate inflammatory signaling associated with enhanced T-cell lymphoproliferation. This review will summarize our current understanding of the pX latency-maintenance factors of HTLV-1 and HTLV-2 and discuss how these products may contribute to the differences in pathogenicity between the human PTLVs.

中文翻译：

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HTLV-1 和 HTLV-2 的消音器：pX 编码的延迟维护因素

在灵长类 T 细胞嗜淋巴细胞病毒 (PTLV) 家族的成员中，只有人类 T 细胞白血病病毒 1 型 (HTLV-1) 会导致人类疾病——作为成人 T 细胞白血病/淋巴瘤 (ATLL) 的病原体)、HTLV-1 相关脊髓病/热带痉挛性下肢轻瘫 (HAM/TSP) 和其他自身炎症性疾病。尽管具有显着的基因组组织和结构相似性，但密切相关的人类 T 细胞嗜淋巴细胞病毒 2 型 (HTLV-2) 被认为是无病原性的，并且与某些感染患者的良性淋巴增生和轻度神经系统症状有关。原病毒基因表达的沉默和潜伏期的维持对于体内持续感染的建立至关重要。HTLV-1 和 HTLV-2 的保守 pX 序列编码几种辅助因子，这些因子已被证明对原病毒基因表达负调控，同时激活宿主细胞增殖和促存活途径。特别是，ORF-II 蛋白 HTLV-1 p30II 和 HTLV-2 p28II 抑制来自病毒启动子的税收依赖性反式激活，而 p30II 也抑制 PU.1 介导的炎症信号传导，不同程度地增强 p53 调节的表达代谢/促存活基因，并诱导淋巴增殖，促进有丝分裂前病毒复制。HTLV-1 p13II 蛋白的泛素化形式定位于核斑点并通过病毒反式激活因子 Tax 干扰 p300 共激活因子的募集。更多，反义编码的 HTLV-1 HBZ 和 HTLV-2 APH-2 蛋白和 mRNA 负向调节税收依赖性前病毒基因表达并激活与增强的 T 细胞淋巴细胞增殖相关的炎症信号传导。本综述将总结我们目前对 HTLV-1 和 HTLV-2 的 pX 延迟维持因素的理解，并讨论这些产品如何导致人类 PTLV 之间的致病性差异。