寨卡病毒（Zika virus，简称ZIKV）是一种隶属黄病毒科（Flaviviridae）、黄病毒属（Flavivirus）的单股正链RNA病毒。流行病学数据深刻揭示，ZIKV感染不仅触发热病，更与新生儿先天性小头畸形以及成人格林-巴雷综合征（Guillain-Barré Syndrome，GBS）存在紧密联系。然而，时至今日，我们仍缺乏针对这一病毒的预防疫苗或有效的抗病毒药物。因此，深入探索ZIKV的致病机制，特别是其与宿主间的相互作用，对于开发针对性的预防和治疗策略至关重要。

通常，ZIKV RNA的翻译过程是由其5’末端的帽子结构所引导，协助核糖体进行准确识别并启动翻译过程。但值得注意的是，2019年的研究提出了一个新颖的观点：ZIKV能够摆脱对基因组5’末端帽子的依赖，独立进行翻译起始。这一突破性的发现归因于ZIKV 5’非编码区（untranslated region, UTR）所具备的内部核糖体进入位点（internal ribosomal entry site，IRES）功能。这一发现使我们不得不重新审视ZIKV的翻译起始机制，并深入探究其与宿主细胞间的微妙互动。

在细胞内，RNA病毒扩增时会与一系列细胞内的IRES反式作用因子（IRES transacting factors，ITAFs）协同工作。其中，多聚嘧啶结合蛋白1（polypyrimidine tract binding protein 1，PTBP1）作为被广泛研究的ITAFs之一，其在病毒IRES的调控中起着不可或缺的正向作用。为了深入探索PTBP1与ZIKV 5’UTR中IRES元件的潜在联系，我们采用了tRSA RNA pull down结合LC-MS/MS分析技术，成功鉴定出PTBP1与ZIKV 5’UTR的紧密结合。进一步通过双荧光素酶报告基因实验，我们观察到PTBP1的过表达显著促进了ZIKV 5’UTR中IRES元件介导的翻译起始；反之，当PTBP1表达被抑制时，IRES介导的翻译起始则明显减弱。此外，感染实验也验证了这一点：PTBP1的过表达显著提升了ZIKV病毒的合成，而PTBP1的低表达则导致病毒合成减少。综上所述，我们确信PTBP1对ZIKV 5’UTR中的IRES元件具有正向调控作用。

Zika virus (ZIKV) is a single-stranded positive-sense RNA virus belonging to the Flaviviridae family and the Flavivirus genus. Epidemiological data have profoundly revealed that ZIKV infection not only triggers fever but is also closely associated with congenital microcephaly in newborns and Guillain-Barré Syndrome (GBS) in adults. However, to date, we still lack preventive vaccines or effective antiviral drugs against this virus. Therefore, a deeper exploration of the pathogenic mechanism of ZIKV, particularly its interaction with the host, is crucial for developing targeted prevention and treatment strategies.

Typically, the translation process of ZIKV RNA is guided by its 5' terminal cap structure, which assists ribosomes in accurately recognizing and initiating the translation process. However, it is noteworthy that a 2019 study proposed a novel viewpoint: ZIKV can initiate translation independently, without relying on the 5' terminal cap of its genome. This groundbreaking discovery is attributed to the internal ribosomal entry site (IRES) function possessed by the 5' untranslated region (UTR) of ZIKV. This finding prompts us to re-examine the translation initiation mechanism of ZIKV and delve deeper into its delicate interactions with host cells.

Within cells, RNA viruses collaborate with a series of intracellular IRES transacting factors (ITAFs) during amplification. Among them, polypyrimidine tract binding protein 1 (PTBP1), one of the most widely studied ITAFs, plays an indispensable positive role in regulating viral IRES. To further explore the potential link between PTBP1 and the IRES element in ZIKV 5' UTR, we employed the tRSA RNA pull-down technique combined with LC-MS/MS analysis, successfully identifying the tight binding between PTBP1 and ZIKV 5' UTR. Through dual-luciferase reporter gene experiments, we observed that overexpression of PTBP1 significantly promoted the translation initiation mediated by the IRES element in ZIKV 5' UTR. Conversely, when PTBP1 expression was inhibited, IRES-mediated translation initiation was significantly weakened. Additionally, infection experiments also validated this: overexpression of PTBP1 significantly enhanced ZIKV virus synthesis, while low expression of PTBP1 led to reduced virus synthesis. In conclusion, we are convinced that PTBP1 positively regulates the IRES element in ZIKV 5' UTR.