Intracellular Low Iron Exerts Anti-BK Polyomavirus Effect by Inhibiting the Protein Synthesis of Exogenous Genes.
Intracellular Low Iron Exerts Anti-BK Polyomavirus Effect by Inhibiting the Protein Synthesis of Exogenous Genes.
复制标题
细胞内低铁通过抑制外源基因蛋白质合成发挥抗BK多瘤病毒作用
DOI：
10.1128/spectrum.01094-21
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发表时间：
2021-12-22
影响因子：
3.7
通讯作者：
Zhu T
中科院分区：
文献类型：
--
作者：
Sun J;Shi Y;Shi H;Hou Y;Hu C;Zeng Y;Wu G;Zhu T
BKPyV对免疫功能低下患者的健康构成严重威胁，目前没有治疗药物。了解病毒与细胞内环境之间的关系有助于发现抗病毒靶点。BK多瘤病毒（BK Polyomavirus，BKPyV）是一种小的双链DNA病毒，广泛存在于人体内，对免疫功能低下的个体尤为重要。BKPyV的抗病毒治疗是迫切需要的。细胞内铁在许多病毒感染中具有重要作用，但其对BKPyV和复制的贡献尚未被探索。在这项研究中，我们探讨了BKPyV感染和细胞内铁之间的相互作用以及铁耗竭对BKPyV感染的抑制作用。通过创造低细胞内铁环境，我们证明了铁螯合诱导的铁耗竭抑制原代肾小管上皮细胞（RPTECs）和膀胱癌细胞（TCCs）中的BKPyV感染。BKPyV进入细胞核后，铁耗竭产生抑制作用，这可能是由于铁耗竭抑制外源基因在细胞中的蛋白质合成。对铁调节病毒感染的靶蛋白的进一步探索可能用于开发迫切需要的抗BKPyV疗法的新策略。重要性BKPyV对免疫功能低下患者的健康构成严重威胁，目前没有治疗药物。了解病毒与细胞内环境之间的关系有助于发现抗病毒靶点。我们在这里证明，BKPyV在低铁环境的细胞中被抑制。我们还发现，铁螯合诱导的铁耗竭抑制病毒和外源性蛋白质的合成。进一步探索铁调节的靶蛋白可能在开发针对BKPyV和其他病毒的新药方面具有巨大潜力。
BKPyV poses a serious threat to the health of immunocompromised patients, and there are currently no curative drugs. Understanding the relationship between the virus and intracellular environment contributes to the discovery of antiviral targets. ABSTRACT BK polyomavirus (BKPyV) is a small double-stranded DNA virus and ubiquitous human pathogen that particularly affects immunocompromised individuals. Antiviral therapy for BKPyV is urgently needed. Intracellular irons have an important role in many viral infections, yet its contribution to BKPyV and replication has not been explored. In this study, we explored the interaction between BKPyV infection and intracellular iron and the inhibitory effect of iron depletion on BKPyV infection. By creating a low-intracellular-iron environment, we demonstrated that the iron-chelating-induced iron depletion inhibits BKPyV infection in primary renal tubular epithelial cells (RPTECs) and urinary bladder cancer cells (TCCSUP cells). Iron depletion exerts an inhibitory effect after BKPyV enters the nucleus, which might be due to the inhibition of the protein synthesis of exogenous genes in iron-depleted cells. Further exploration of the target proteins of iron-regulating viral infection could potentially be used to develop new strategies for urgently needed anti-BKPyV therapies. IMPORTANCE BKPyV poses a serious threat to the health of immunocompromised patients, and there are currently no curative drugs. Understanding the relationship between the virus and intracellular environment contributes to the discovery of antiviral targets. We demonstrate here that BKPyV is inhibited in cells with a low-iron environment. We also find that iron-chelating-induced iron depletion inhibits viral and exogenous protein synthesis. Further exploration of the target proteins of iron regulation could have great potential in developing new drugs against BKPyV and other viruses.