TY - JOUR
T1 - Phosphatidic acid phosphatase 1 impairs SARS-CoV-2 replication by affecting the glycerophospholipid metabolism pathway
AU - Yan, Bingpeng
AU - Yuan, Shuofeng
AU - Cao, Jianli
AU - Fung, Kingchun
AU - Lai, Pok Man
AU - Yin, Feifei
AU - Sze, Kong Hung
AU - Qin, Zhenzhi
AU - Xie, Yubin
AU - Ye, Zi Wei
AU - Yuen, Terrence Tsz Tai
AU - Chik, Kenn Ka Heng
AU - Tsang, Jessica Oi Ling
AU - Zou, Zijiao
AU - Chan, Chris Chun Yiu
AU - Luo, Cuiting
AU - Cai, Jian Piao
AU - Chan, Kwok Hung
AU - Chung, Tom Wai Hing
AU - Tam, Anthony Raymond
AU - Chu, Hin
AU - Jin, Dong Yan
AU - Hung, Ivan Fan Ngai
AU - Yuen, Kwok Yung
AU - Kao, Richard Yi Tsun
AU - Chan, Jasper Fuk Woo
N1 - Publisher Copyright:
© The author(s).
PY - 2022
Y1 - 2022
N2 - Viruses exploit the host lipid metabolism machinery to achieve efficient replication. We herein characterize the lipids profile reprogramming in vitro and in vivo using liquid chromatography-mass spectrometry-based untargeted lipidomics. The lipidome of SARS-CoV-2-infected Caco-2 cells was markedly different from that of mock-infected samples, with most of the changes involving downregulation of ceramides. In COVID-19 patients’ plasma samples, a total of 54 lipids belonging to 12 lipid classes that were significantly perturbed compared to non-infected control subjects’ plasma samples were identified. Among these 12 lipid classes, ether-linked phosphatidylcholines, ether-linked phosphatidylethanolamines, phosphatidylcholines, and ceramides were the four most perturbed. Pathway analysis revealed that the glycerophospholipid, sphingolipid, and ether lipid metabolisms pathway were the most significantly perturbed host pathways. Phosphatidic acid phosphatases (PAP) were involved in all three pathways and PAP-1 deficiency significantly suppressed SARS-CoV-2 replication. siRNA knockdown of LPIN2 and LPIN3 resulted in significant reduction of SARS-CoV-2 load. In summary, these findings characterized the host lipidomic changes upon SARS-CoV-2 infection and identified PAP-1 as a potential target for intervention for COVID-19.
AB - Viruses exploit the host lipid metabolism machinery to achieve efficient replication. We herein characterize the lipids profile reprogramming in vitro and in vivo using liquid chromatography-mass spectrometry-based untargeted lipidomics. The lipidome of SARS-CoV-2-infected Caco-2 cells was markedly different from that of mock-infected samples, with most of the changes involving downregulation of ceramides. In COVID-19 patients’ plasma samples, a total of 54 lipids belonging to 12 lipid classes that were significantly perturbed compared to non-infected control subjects’ plasma samples were identified. Among these 12 lipid classes, ether-linked phosphatidylcholines, ether-linked phosphatidylethanolamines, phosphatidylcholines, and ceramides were the four most perturbed. Pathway analysis revealed that the glycerophospholipid, sphingolipid, and ether lipid metabolisms pathway were the most significantly perturbed host pathways. Phosphatidic acid phosphatases (PAP) were involved in all three pathways and PAP-1 deficiency significantly suppressed SARS-CoV-2 replication. siRNA knockdown of LPIN2 and LPIN3 resulted in significant reduction of SARS-CoV-2 load. In summary, these findings characterized the host lipidomic changes upon SARS-CoV-2 infection and identified PAP-1 as a potential target for intervention for COVID-19.
KW - COVID-19
KW - SARS-CoV-2
KW - lipidomics
KW - phosphatidic acid phosphatases
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U2 - 10.7150/ijbs.73057
DO - 10.7150/ijbs.73057
M3 - Article
C2 - 35874954
AN - SCOPUS:85134609734
SN - 1449-2288
VL - 18
SP - 4744
EP - 4755
JO - International Journal of Biological Sciences
JF - International Journal of Biological Sciences
IS - 12
ER -