2. Academic Validation
  3. Targeting lysophospholipid acid receptor 1 and ROCK kinases promotes antiviral innate immunity

Targeting lysophospholipid acid receptor 1 and ROCK kinases promotes antiviral innate immunity

  • Sci Adv. 2021 Sep 17;7(38):eabb5933. doi: 10.1126/sciadv.abb5933.
Chi Zhang 1 2,  Weiyun Li 2 3,  Xiaobo Lei 4,  Zhenfei Xie 2,  Linlin Qi 5,  Hui Wang 6,  Xia Xiao 4,  Jun Xiao 2,  Yuxiao Zheng 2,  Chen Dong 2,  Xin Zheng 2,  Shiyang Chen 1 2,  Jianfeng Chen 2,  Bing Sun 2,  Jun Qin 6,  Qiwei Zhai 6,  Jinsong Li 2,  Bin Wei 5 7 8,  Jianwei Wang 4,  Hongyan Wang 1 2 9
Affiliations

Affiliations

  • 1 School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.
  • 2 State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
  • 3 School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
  • 4 National Health Commission of the People's Republic of China, Key Laboratory of System Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • 5 State Key Laboratory of Virology, Wuhan Institute of Virology, Wuhan, China.
  • 6 CAS Key Laboratory of Nutrition, Metabolism and Food Safety, CAS Center for Excellence in Molecular Cell Sciences, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China.
  • 7 College of Life Sciences, Shanghai University, Shanghai 200444, China.
  • 8 Cancer Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
  • 9 Bio-Research Innovation Center Suzhou, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Suzhou, Jiangsu 215121, China.
PMID: 34533996 DOI: 10.1126/sciadv.abb5933
Abstract

Growing evidence indicates the vital role of lipid metabolites in innate immunity. The lipid lysophosphatidic acid (LPA) concentrations are enhanced in patients upon HCV or SARS-CoV-2 Infection, but the function of LPA and its receptors in innate immunity is largely unknown. Here, we found that viral Infection promoted the G protein–coupled receptor LPA1 expression, and LPA restrained type I/III interferon production through LPA1. Mechanistically, LPA1 signaling activated ROCK1/2, which phosphorylated IRF3 Ser97 to suppress IRF3 activation. Targeting LPA1 or ROCK in macrophages, fibroblasts, epithelial cells, and LPA1 conditional KO mice promoted interferon-induced clearance of multiple viruses. LPA1 was colocalized with the receptor ACE2 in lung and intestine. Together with previous findings that LPA1 and ROCK1/2 promoted vascular leaking or lung fibrosis, we propose that the current available preclinical drugs targeting the LPA1-ROCK module might protect from SARS-CoV-2 or various virus infections in the intestine or lung.

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