Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Manganese Mediates its Antiviral Functions in a cGAS-STING Pathway Independent Manner

Shaohua Sun
,
Xulin Xu
,
Ming Qiu
,
Sen Jiang
,
Qi Cao
,
Jia Luo
,
Tangjie Zhang
ORCID logo ,
Nanhua Chen
,
Wanglong Zheng
,
Francois Meurens
ORCID logo ,
Zongping Liu
* ORCID logo ,
Jianzhong Zhu
* ORCID logo
Version 1 : Received: 4 February 2023 / Approved: 6 February 2023 / Online: 6 February 2023 (10:01:21 CET)

A peer-reviewed article of this Preprint also exists.

Sun, S.; Xu, Y.; Qiu, M.; Jiang, S.; Cao, Q.; Luo, J.; Zhang, T.; Chen, N.; Zheng, W.; Meurens, F.; Liu, Z.; Zhu, J. Manganese Mediates Its Antiviral Functions in a cGAS-STING Pathway Independent Manner. Viruses 2023, 15, 646. Sun, S.; Xu, Y.; Qiu, M.; Jiang, S.; Cao, Q.; Luo, J.; Zhang, T.; Chen, N.; Zheng, W.; Meurens, F.; Liu, Z.; Zhu, J. Manganese Mediates Its Antiviral Functions in a cGAS-STING Pathway Independent Manner. Viruses 2023, 15, 646.

Abstract

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 innate immune DNA sensing cGAS-STING pathway and subsequent anti-DNA virus function. However, whether Mn2+ mediates host defense against RNA viruses is still unclear. In the current study, we demonstrated that Mn2+ exhibited antiviral effects against various animal and human viruses including RNA viruses such as PRRSVs and the VSV as well as a DNA virus such as the HSV1 in a dose-dependent manner. Moreover, cGAS and STING were both investigated in the Mn2+ mediated antiviral roles using the knockout cells made by CRISPR-Cas9 approach. Unexpectedly, the results revealed that neither cGAS knockout nor STING knockout had any effect on Mn2+ mediated antiviral functions. Nevertheless, we verified that Mn2+ promoted the activation of cGAS-STING signaling pathway. These findings suggest that Mn2+ has broad spectrum antiviral activities in a cGAS-STING pathway independent manner. This study also provides significant insights into redundant mechanisms participating in the Mn2+ antiviral functions and also indicates new target for Mn2+ antiviral therapeutics.

Keywords

manganese; cGAS-STING pathway; RNA virus; antiviral function; redundant mechanisms

Subject

Biology and Life Sciences, Immunology and Microbiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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