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A multi-omics investigation of the composition and function of extracellular vesicles along the temporal trajectory of COVID-19.
Lam, Sin Man; Zhang, Chao; Wang, Zehua; Ni, Zhen; Zhang, Shaohua; Yang, Siyuan; Huang, Xiahe; Mo, Lesong; Li, Jie; Lee, Bernett; Mei, Mei; Huang, Lei; Shi, Ming; Xu, Zhe; Meng, Fan-Ping; Cao, Wen-Jing; Zhou, Ming-Ju; Shi, Lei; Chua, Gek Huey; Li, Bowen; Cao, Jiabao; Wang, Jun; Bao, Shilai; Wang, Yingchun; Song, Jin-Wen; Zhang, Fujie; Wang, Fu-Sheng; Shui, Guanghou.
  • Lam SM; State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
  • Zhang C; LipidALL Technologies Company Limited, Changzhou, China.
  • Wang Z; Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China.
  • Ni Z; State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
  • Zhang S; University of the Chinese Academy of Sciences, Beijing, China.
  • Yang S; State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
  • Huang X; University of the Chinese Academy of Sciences, Beijing, China.
  • Mo L; State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
  • Li J; Laboratory of Infectious Diseases Center, Beijing Ditan Hospital Capital Medical University, Beijing, China.
  • Lee B; State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
  • Mei M; State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
  • Huang L; University of the Chinese Academy of Sciences, Beijing, China.
  • Shi M; State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
  • Xu Z; University of the Chinese Academy of Sciences, Beijing, China.
  • Meng FP; Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
  • Cao WJ; State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
  • Zhou MJ; Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China.
  • Shi L; Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China.
  • Chua GH; Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China.
  • Li B; Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China.
  • Cao J; Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China.
  • Wang J; Department of Clinical Medicine, Bengbu Medical College, Anhui, China.
  • Bao S; Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China.
  • Wang Y; Department of Clinical Medicine, Bengbu Medical College, Anhui, China.
  • Song JW; Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China.
  • Zhang F; LipidALL Technologies Company Limited, Changzhou, China.
  • Wang FS; LipidALL Technologies Company Limited, Changzhou, China.
  • Shui G; University of the Chinese Academy of Sciences, Beijing, China.
Nat Metab ; 3(7): 909-922, 2021 07.
Article in English | MEDLINE | ID: covidwho-1279905
ABSTRACT
Exosomes represent a subtype of extracellular vesicle that is released through retrograde transport and fusion of multivesicular bodies with the plasma membrane1. Although no perfect methodologies currently exist for the high-throughput, unbiased isolation of pure plasma exosomes2,3, investigation of exosome-enriched plasma fractions of extracellular vesicles can confer a glimpse into the endocytic pathway on a systems level. Here we conduct high-coverage lipidomics with an emphasis on sterols and oxysterols, and proteomic analyses of exosome-enriched extracellular vesicles (EVs hereafter) from patients at different temporal stages of COVID-19, including the presymptomatic, hyperinflammatory, resolution and convalescent phases. Our study highlights dysregulated raft lipid metabolism that underlies changes in EV lipid membrane anisotropy that alter the exosomal localization of presenilin-1 (PS-1) in the hyperinflammatory phase. We also show in vitro that EVs from different temporal phases trigger distinct metabolic and transcriptional responses in recipient cells, including in alveolar epithelial cells, which denote the primary site of infection, and liver hepatocytes, which represent a distal secondary site. In comparison to the hyperinflammatory phase, EVs from the resolution phase induce opposing effects on eukaryotic translation and Notch signalling. Our results provide insights into cellular lipid metabolism and inter-tissue crosstalk at different stages of COVID-19 and are a resource to increase our understanding of metabolic dysregulation in COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Metabolomics / Extracellular Vesicles / Lipidomics / SARS-CoV-2 / COVID-19 Type of study: Observational study / Risk factors Limits: Humans Language: English Journal: Nat Metab Year: 2021 Document Type: Article Affiliation country: S42255-021-00425-4

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Metabolomics / Extracellular Vesicles / Lipidomics / SARS-CoV-2 / COVID-19 Type of study: Observational study / Risk factors Limits: Humans Language: English Journal: Nat Metab Year: 2021 Document Type: Article Affiliation country: S42255-021-00425-4