Herpes Simplex Virus 1 Induces Microglia Gasdermin D-Dependent Pyroptosis Through Activating the NLR Family Pyrin Domain Containing 3 Inflammasome

Hu, Xiao1,2,3,4,5,6; Zeng, Qiongzhen1,2,3,5,6; Xiao, Ji1,2,3,5,6; Qin, Shurong1,2,3,4,5,6; Wang, Yuan1,2,3,5,6; Shan, Tianhao1,2,3,5,6; Hu, Di1,2,3,4,5,6; Zhu, Yexuan1,2,3,5,6; Liu, Kaisheng7; Zheng, Kai8; Wang, Yifei1,2,3,5,6; Ren, Zhe1,2,3,5,6

2022-03-21

10.3389/fmicb.2022.838808

FRONTIERS IN MICROBIOLOGY   影响因子和分区

1664-302X

Herpes simplex virus type 1 (HSV-1) is a highly prevalent virus in humans and causes severe forms of inflammation, such as herpes simplex encephalitis (HSE). Pyroptosis is a new inflammatory cell death triggered by inflammasome and cysteine-requiring aspartate protease-1 (caspase-1) activation. Nonetheless, HSV-1 induces encephalitis, and cell death mechanisms are not understood. In this study, we confirmed for the first time that the DNA virus HSV-1 triggers Gasdermin D-dependent pyroptosis by activating NLR family pyrin domain containing 3 (NLRP3) inflammasomes in mouse microglia, leading to mature IL-1 beta production and active caspase-1 (p10) release. Inhibition of microglial NLRP3 inflammasome activation suppressed HSV-1-induced Gasdermin D-dependent pyroptosis. In addition, NLRP3 and IL-1 beta expression levels were significantly increased in the mouse model of herpes simplex encephalitis compared with normal mice without viral infection. Collectively, our data revealed that the activation of inflammasomes and GSDMD-dependent pyroptosis is the mechanism of HSV-1 inducing inflammation and provides treatment targets for viral inflammation.

pyroptosis inflammation NLRP3 inflammasome Gasdermin D Herpes simplex virus type 1 herpes simplex virus encephalitis

SCI

英语

其他

National Natural Science Foundation of China[81872908,82072274] ; Natural Science Foundation of Guangdong Province[2019A1515010046] ; Science and Technology Foundation of Shenzhen[JCYJ20200109144410181]

Microbiology

Microbiology

WOS:000780022600001

FRONTIERS MEDIA SA

Web of Science

1.Jinan Univ, Inst Biomed, Coll Life Sci & Technol, Guangzhou Jinan Biomed Res & Dev Ctr, Guangzhou, Peoples R China
2.Jinan Univ, Key Lab Virol Guangdong, Guangzhou, Peoples R China
3.Jinan Univ, Coll Life Sci & Technol, Dept Cell Biol, Guangzhou, Peoples R China
4.Jinan Univ, Coll Pharm, Guangzhou, Peoples R China
5.Jinan Univ, Guangdong Prov Key Lab Bioengn Med, Guangzhou, Peoples R China
6.Jinan Univ, Natl Engn Res Ctr Genet Med, Guangzhou, Peoples R China
7.Jinan Univ, Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Clin Med Coll 2, Shenzhen, Peoples R China
8.Shenzhen Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, Shenzhen, Peoples R China

Hu, Xiao,Zeng, Qiongzhen,Xiao, Ji,et al. Herpes Simplex Virus 1 Induces Microglia Gasdermin D-Dependent Pyroptosis Through Activating the NLR Family Pyrin Domain Containing 3 Inflammasome[J]. FRONTIERS IN MICROBIOLOGY,2022,13.

Hu, Xiao.,Zeng, Qiongzhen.,Xiao, Ji.,Qin, Shurong.,Wang, Yuan.,...&Ren, Zhe.(2022).Herpes Simplex Virus 1 Induces Microglia Gasdermin D-Dependent Pyroptosis Through Activating the NLR Family Pyrin Domain Containing 3 Inflammasome.FRONTIERS IN MICROBIOLOGY,13.

Hu, Xiao,et al."Herpes Simplex Virus 1 Induces Microglia Gasdermin D-Dependent Pyroptosis Through Activating the NLR Family Pyrin Domain Containing 3 Inflammasome".FRONTIERS IN MICROBIOLOGY 13(2022).