| First Author | Zhang C | Year | 2021 |
| Journal | Sci Adv | Volume | 7 |
| Issue | 38 | Pages | eabb5933 |
| PubMed ID | 34533996 | Mgi Jnum | J:311757 |
| Mgi Id | MGI:6764162 | Doi | 10.1126/sciadv.abb5933 |
| Citation | Zhang C, et al. (2021) Targeting lysophospholipid acid receptor 1 and ROCK kinases promotes antiviral innate immunity. Sci Adv 7(38):eabb5933 |
| abstractText | 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 proteinâcoupled 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. |
