Zinc-dependent viral proteins rely on intracellular zinc homeostasis for successful completion of infectious life-cycle. Here, we report that the intracellular labile zinc levels were elevated at early stages of dengue virus (DENV) infection in hepatic cells and this increase in free zinc was abolished in cells infected with UV-inactivated virus or with a DENV replication inhibitor implicating a role for zinc homeostasis in viral RNA replication. This change in free zinc was mediated by zinc transporter, ZIP8, as siRNA-mediated knockdown of ZIP8 resulted in abrogation of increase in free zinc levels leading to significant reduction in DENV titers suggesting a crucial role for ZIP8 in early stages of DENV replication. Furthermore, elevated free zinc levels correlated with high copy numbers of dengue genome in peripheral blood leukocytes obtained from dengue patients compared to healthy controls suggesting a critical role for zinc homeostasis in dengue infection.

中文翻译：

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登革热病毒复制通过调节 ZIP8 增强了不稳定的锌池

锌依赖性病毒蛋白依赖于细胞内锌稳态来成功完成感染性生命周期。在这里，我们报告说，在肝细胞中登革热病毒 (DENV) 感染的早期阶段，细胞内不稳定的锌水平升高，而这种游离锌的增加在感染紫外线灭活病毒或 DENV 复制抑制剂的细胞中被消除，这与一种作用有关。用于病毒 RNA 复制中的锌稳态。游离锌的这种变化是由锌转运蛋白 ZIP8 介导的，因为 siRNA 介导的 ZIP8 敲低导致游离锌水平的增加消失，导致 DENV 滴度显着降低，这表明 ZIP8 在 DENV 复制的早期阶段起着至关重要的作用。此外，