School of Life Sciences, Anhui Agricultural University, Hefei 230036, China; Anhui International Joint Research and Developmental Center of Sericulture Resources Utilization, Hefei 230036, China.
National Navel Orange Engineering and Technology Research Center, Gannan Normal University, Ganzhou 341000, China.
Int J Biol Macromol. 2022 Sep 30;217:842-852. doi: 10.1016/j.ijbiomac.2022.07.169. Epub 2022 Jul 26.
Ferritin heavy-chain homolog (FerHCH), an iron-binding protein, plays an important role in the host defense against oxidative stress and pathogen infections. In our previous research, Bombyx mori native ferritin had an interaction with B. mori nucleopolyhedrovirus (BmNPV). However, the underlying molecular mechanism of single ferritin homolog responses to BmNPV infection remains unclear. In this study, we found that BmNPV titer and B. mori FerHCH (BmFerHCH) expression were positively correlated with the ferric iron concentration. We performed RNA interference (RNAi) and overexpression experiments to investigate the effects of BmFerHCH on BmNPV proliferation. BmFerHCH knockdown suppressed BmNPV proliferation in vivo and in vitro, whereas BmFerHCH overexpression facilitated BmNPV proliferation. In addition, the oxidative stress level was increased significantly in BmN cells after budded virus infection, while BmFerHCH could neutralize the increased ROS production induced by BmNPV. Of note, we found that ROS was involved in BmNPV-induced apoptosis. Through inhibiting ROS, apoptosis was suppressed by BmFerHCH, whereas BmFerHCH knockdown facilitated apoptosis. Therefore, we hypothesize that BmFerHCH-mediated inhibition of virus-induced apoptosis depends on suppressing ROS accumulation and, thereby, facilitates virus replication. These results suggest that BmFerHCH plays an important role in facilitating BmNPV proliferation and modulating BmFerHCH is potential strategy for studying host-pathogen interactions.
铁蛋白重链同源物（FerHCH）是一种铁结合蛋白，在宿主抵御氧化应激和病原体感染中发挥重要作用。在我们之前的研究中，家蚕天然铁蛋白与家蚕核型多角体病毒（BmNPV）相互作用。然而，单一 FerHCH 同源物对 BmNPV 感染的反应的潜在分子机制尚不清楚。在本研究中，我们发现 BmNPV 效价和家蚕 FerHCH（BmFerHCH）表达与三价铁浓度呈正相关。我们进行了 RNA 干扰（RNAi）和过表达实验，以研究 BmFerHCH 对 BmNPV 增殖的影响。BmFerHCH 敲低抑制了体内和体外的 BmNPV 增殖，而 BmFerHCH 过表达促进了 BmNPV 的增殖。此外，在芽生病毒感染后，BmN 细胞中的氧化应激水平显著增加，而 BmFerHCH 可以中和 BmNPV 诱导的 ROS 产生增加。值得注意的是，我们发现 ROS 参与了 BmNPV 诱导的细胞凋亡。通过抑制 ROS，BmFerHCH 抑制了细胞凋亡，而 BmFerHCH 敲低则促进了细胞凋亡。因此，我们假设 BmFerHCH 介导的抑制病毒诱导的细胞凋亡依赖于抑制 ROS 的积累，从而促进病毒复制。这些结果表明，BmFerHCH 在促进 BmNPV 增殖中发挥重要作用，调节 BmFerHCH 可能是研究宿主-病原体相互作用的潜在策略。
