首页|STING strengthens host anti-hantaviral immunity through an interferon-independent pathway

STING strengthens host anti-hantaviral immunity through an interferon-independent pathway

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Hantaan virus(HTNV),the prototype virus of hantavirus,could escape innate immunity by restraining type Ⅰ interferon(IFN)responses.It is largely unknown whether there existed other efficient anti-hantaviral tactics in host cells.Here,we demonstrate that the stimulator of interferon genes(STING)strengthens the host IFN-independent anti-hantaviral immunity.HTNV infection activates RIG-I through IRE1-XBP 1-mediated ER stress,which further facilitates the subcellular translocation and activation of STING.During this process,STING triggers cellular autophagy by interacting with Rab7A,thus restricting viral replication.To note,the anti-hantaviral effects of STING are independent of canonical IFN signaling.Additionally,neither application of the pharmacological antagonist nor the agonist targeting STING could improve the outcomes of nude mice post HTNV challenge in vivo.However,the administration of plasmids exogenously expressing the mutant C-terminal tail(ACTT)STING,which would not trigger the type Ⅰ IFN responses,protected the nude mice from lethal HTNV infection.In summary,our research revealed a novel antiviral pathway through the RIG-I-STING-autophagy pathway,which offered novel therapeutic strategies against hantavirus infection.

Hantaan virus(HTNV)IRE1RIG-ISTINGAutophagyInnate immunity

Kerong Wang、Jian Zhang、Yongheng Yang、Yue Si、Ziqing Zhou、Xudong Zhu、Sushan Wu、He Liu、Hui Zhang、Liang Zhang、Linfeng Cheng、Wei Ye、Xin Lv、Yingfeng Lei、Xijing Zhang、Shilin Cheng、Lixin Shen、Fanglin Zhang、Hongwei Ma

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College of Life Sciences,Northwest University,Xi'an 710069,China

Department of Microbiology,School of Basic Medicine,Fourth Military Medical University,Xi'an 710032,China

College of Medicine,Yan'an University,Yan'an 716000,China

Department of Anesthesiology & Critical Care Medicine,Xijing Hospital,Fourth Military Medical University,Xi'an,710032,China

Medical Genetics and Developmental Biology,School of Basic Medicine,Fourth Military Medical University,Xi'an 710032,China

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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaKey Research and Development Program of ShaanxiKey Research and Development Program of Shaanxi

3197014882172272822023672021ZDLSF01-022021ZDLSF01-05

2023

10.1016/j.virs.2023.06.006

中国病毒学
中国科学院武汉病毒研究所，中国微生物学会

中国病毒学

CSTPCDCSCD
影响因子：0.393
ISSN：1674-0769
年,卷(期)：2023.38(4)
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