The source of RNA-seq data.

HTLV-1 is an oncovirus that encodes a transactivator Tax and a regulatory gene HBZ. HTLV-1 early or infectious replication depends on Tax; during HTLV-1 late infection, HBZ plays a crucial role in driving the proliferation of infected cells and maintaining viral persistence. The biphasic replication pattern of HTLV-1 dictated by Tax and HBZ represents a result of viral host adaptation, but how HTLV-1 coordinates Tax and HBZ expression to facilitate early and late infection remains elusive. Here we reveal that HBZ RNA splicing exhibits distinct patterns in Tax+ and Tax- HTLV-1 infected cells. We demonstrate that Tax interacts with the host spliceosome and inhibits HBZ splicing by competitively binding splicing factors including WDR83 and GPATCH1. As a result, Tax confers a natural constraint on HBZ, counterbalancing its anti-replication effect at HTLV-1 early infection, while unleashing HBZ to drive HTLV-1 mitotic propagation during late infection. The splicing-dependent restriction of HBZ by Tax thus represents a critical interplay central to HTLV-1 persistence.

人类T细胞白血病病毒1型（HTLV-1）是一种致癌病毒（oncovirus），其基因组编码反式激活蛋白Tax（transactivator Tax）与调控基因HBZ（HBZ）。HTLV-1的早期感染与复制依赖于Tax；在HTLV-1感染后期，HBZ在驱动受感染细胞增殖并维持病毒持久性方面发挥关键作用。由Tax与HBZ共同调控的HTLV-1双相复制模式，是病毒宿主适应的产物，但HTLV-1如何协调Tax与HBZ的表达以促进感染的早晚期进程，目前仍难以阐明。本研究揭示，HBZ的RNA剪接（RNA splicing）在Tax阳性（Tax+）与Tax阴性（Tax-）的HTLV-1感染细胞中呈现显著差异的模式。实验证实，Tax可与宿主剪接体（spliceosome）相互作用，并通过竞争性结合包括WDR83与GPATCH1在内的剪接因子（splicing factors），抑制HBZ的剪接过程。由此，Tax对HBZ施加了天然的约束作用，抵消其在HTLV-1感染早期的抗复制效应；而在感染后期则解除对HBZ的抑制，使其驱动HTLV-1的有丝分裂增殖。因此，Tax依赖剪接过程对HBZ的调控作用，是HTLV-1维持病毒持久性的核心相互调控机制。