Targeting lysophospholipid acid receptor 1 and ROCK kinases promotes antiviral innate immunity.
Sci Adv
; 7(38): eabb5933, 2021 Sep 17.
Article
in English
| MEDLINE | ID: covidwho-1440796
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 proteincoupled 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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Language:
English
Journal:
Sci Adv
Year:
2021
Document Type:
Article
Affiliation country:
Sciadv.abb5933
Similar
MEDLINE
...
LILACS
LIS