College Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.
Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou University, Yangzhou 225009, China.
Viruses. 2023 Feb 28;15(3):646. doi: 10.3390/v15030646.
The innate immune system is the first line of host defense sensing viral infection. Manganese (Mn) has recently been found to be involved in the activation of the innate immune DNA-sensing cGAS-STING pathway and subsequent anti-DNA virus function. However, it is still unclear whether Mn mediates host defense against RNA viruses. In this study, we demonstrate that Mn exhibited antiviral effects against various animal and human viruses, including RNA viruses such as PRRSVs and VSV, as well as DNA viruses such as HSV1, in a dose-dependent manner. Moreover, cGAS and STING were both investigated in the Mn mediated antiviral roles using the knockout cells made by the CRISPR-Cas9 approach. Unexpectedly, the results revealed that neither cGAS knockout nor STING knockout had any effect on Mn-mediated antiviral functions. Nevertheless, we verified that Mn promoted the activation of the cGAS-STING signaling pathway. These findings suggest that Mn has broad-spectrum antiviral activities in a cGAS-STING pathway independent manner. This study also provides significant insights into redundant mechanisms participating in the Mn antiviral functions, and also indicates a new target for Mn antiviral therapeutics.
先天免疫系统是宿主防御的第一道防线，能够感知病毒感染。最近发现，锰 (Mn) 参与了先天免疫 DNA 感应 cGAS-STING 途径的激活以及随后的抗 DNA 病毒功能。然而，目前尚不清楚 Mn 是否介导宿主对 RNA 病毒的防御。在这项研究中，我们证明了 Mn 以剂量依赖的方式对各种动物和人类病毒表现出抗病毒作用，包括 RNA 病毒（如 PRRSV 和 VSV）和 DNA 病毒（如 HSV1）。此外，我们还使用 CRISPR-Cas9 方法构建的敲除细胞来研究 cGAS 和 STING 在 Mn 介导的抗病毒作用中的作用。出乎意料的是，结果表明 cGAS 敲除或 STING 敲除对 Mn 介导的抗病毒功能均没有影响。然而，我们验证了 Mn 促进了 cGAS-STING 信号通路的激活。这些发现表明，Mn 具有非依赖 cGAS-STING 通路的广谱抗病毒活性。本研究还为参与 Mn 抗病毒功能的冗余机制提供了重要的见解，并表明 Mn 抗病毒治疗的一个新靶点。
