Lipid droplets fuel SARS-CoV-2 replication and production of inflammatory mediators.
Suelen da Silva Gomes Dias,Vinicius Cardoso Soares,Vinicius Cardoso Soares,André C. Ferreira,Carolina Q. Sacramento,Natalia Fintelman-Rodrigues,Jairo R. Temerozo,Lívia Teixeira,Marcos Alexandre Nunes da Silva,Ester A. Barreto,Mayara Mattos,Caroline S. de Freitas,Isaclaudia G. de Azevedo-Quintanilha,Pedro P.A. Manso,Milene D. Miranda,Marilda M. Siqueira,Eugenio D. Hottz,Eugenio D. Hottz,Camila R. R. Pão,Dumith Chequer Bou-Habib,Debora Ferreira Barreto-Vieira,Fernando A. Bozza,Thiago Moreno L. Souza,Patrícia T. Bozza +23 more
TLDR
The essential role of lipid metabolic reprograming and LD formation in SARS-CoV-2 replication and pathogenesis is demonstrated, opening new opportunities for therapeutic strategies to COVID-19 patients.Abstract:
Viruses are obligate intracellular parasites that make use of the host metabolic machineries to meet their biosynthetic needs. Thus, identifying the host pathways essential for the virus replication may lead to potential targets for therapeutic intervention. The mechanisms and pathways explored by SARS-CoV-2 to support its replication within host cells are not fully known. Lipid droplets (LD) are organelles with major functions in lipid metabolism, energy homeostasis and intracellular transport, and have multiple roles in infections and inflammation. Here we described that monocytes from COVID-19 patients have an increased LD accumulation compared to SARS-CoV-2 negative donors. In vitro, SARS-CoV-2 infection were seen to modulate pathways of lipid synthesis and uptake as monitored by testing for CD36, SREBP-1, PPARγ, and DGAT-1 expression in monocytes and triggered LD formation in different human cell lines. LDs were found in close apposition with SARS-CoV-2 proteins and double-stranded (ds)-RNA in infected Vero cells. Electron microscopy (EM) analysis of SARS-CoV-2 infected Vero cells show viral particles colocalizing with LDs, suggestive that LDs might serve as an assembly platform. Pharmacological modulation of LD formation by inhibition of DGAT-1 with A922500 significantly inhibited SARS-CoV-2 replication as well as reduced production of mediators pro-inflammatory response. Taken together, we demonstrate the essential role of lipid metabolic reprograming and LD formation in SARS-CoV-2 replication and pathogenesis, opening new opportunities for therapeutic strategies to COVID-19.read more
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Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study
Fei Zhou,Ting Yu,Ronghui Du,Guohui Fan,Ying Liu,Zhibo Liu,Jie Xiang,Yeming Wang,Bin Song,Xiaoying Gu,Xiaoying Gu,Lulu Guan,Yuan Wei,Li Hui,Xudong Wu,Jiuyang Xu,Shengjin Tu,Yi Zhang,Hua Chen,Bin Cao +19 more
TL;DR: Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.
Journal ArticleDOI
Monocytes and Macrophages in COVID-19.
TL;DR: In this article, the authors outline current knowledge on monocytes and macrophages in homeostasis and viral infections and summarize concepts and key findings on their role in COVID-19.
Journal ArticleDOI
Dissecting lipid metabolism alterations in SARS-CoV-2.
TL;DR: In this paper, the authors used untargeted metabolomic and lipidomic approaches to provide new insight into the host response to COVID-19 infection and identified numerous circulating lipids that directly correlate to severity of the disease, making lipid metabolism a potential therapeutic target.
Journal ArticleDOI
The role of NSP6 in the biogenesis of the SARS-CoV-2 replication organelle
Simona Ricciardi,A. Guarino,Laura Giaquinto,Elena Polishchuk,Michele Santoro,Giuseppe Di Tullio,Cathal Wilson,Francesco Panariello,Vinicius Cardoso Soares,Suelen da Silva Gomes Dias,J. Santos,Thiago Moreno L. Souza,Giovanna Fusco,Maurizio Viscardi,Sergio Brandi,Patrícia T. Bozza,Roman S. Polishchuk,Rossella Venditti,Maria Antonietta De Matteis +18 more
TL;DR: In this article , the authors identify the viral non-structural proteins (NSPs) that generate the SARS-CoV-2 replication organelle, which is composed of double-membrane vesicles (DMVs) tethered to the endoplasmic reticulum (ER) by thin membrane connectors.
Journal ArticleDOI
The role of NSP6 in the biogenesis of the SARS-CoV-2 replication organelle
S. Ricciardi,A. Guarino,Laura Giaquinto,Elena Polishchuk,Michele Santoro,Giuseppe Di Tullio,Cathal Wilson,Francesco Panariello,Vinicius Cardoso Soares,Suelen da Silva Gomes Dias,J. Santos,Thiago Moreno L. Souza,Giovanna Fusco,Maurizio Viscardi,Sergio Brandi,Patrícia T. Bozza,Roman S. Polishchuk,Rossella Venditti,Maria Antonietta De Matteis +18 more
TL;DR: In this paper , the authors identify the viral non-structural proteins (NSPs) that generate the SARS-CoV-2 replication organelle, which is composed of double-membrane vesicles (DMVs) tethered to the endoplasmic reticulum (ER) by thin membrane connectors.
References
More filters
Journal ArticleDOI
THE USE OF LEAD CITRATE AT HIGH pH AS AN ELECTRON-OPAQUE STAIN IN ELECTRON MICROSCOPY
TL;DR: The stain reported here differs from previous alkaline lead stains in that the chelating agent, citrate, is in sufficient excess to sequester all lead present, and is less likely to contaminate sections.
Journal ArticleDOI
A Novel Coronavirus from Patients with Pneumonia in China, 2019.
Na Zhu,Dingyu Zhang,Wenling Wang,Xingwang Li,Bo Yang,Jingdong Song,Xiang Zhao,Baoying Huang,Weifeng Shi,Roujian Lu,Peihua Niu,Faxian Zhan,Xuejun Ma,Dayan Wang,Wenbo Xu,Wenbo Xu,Guizhen Wu,George F. Gao,Wenjie Tan +18 more
TL;DR: Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily, which is the seventh member of the family of coronaviruses that infect humans.
Journal ArticleDOI
Analyzing real-time PCR data by the comparative C(T) method.
TL;DR: This protocol provides an overview of the comparative CT method for quantitative gene expression studies and various examples to present quantitative gene Expression data using this method.
Journal ArticleDOI
Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.
Fei Zhou,Ting Yu,Ronghui Du,Guohui Fan,Ying Liu,Zhibo Liu,Jie Xiang,Yeming Wang,Bin Song,Xiaoying Gu,Xiaoying Gu,Lulu Guan,Yuan Wei,Li Hui,Xudong Wu,Jiuyang Xu,Shengjin Tu,Yi Zhang,Hua Chen,Bin Cao +19 more
TL;DR: Wang et al. as discussed by the authors used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death, including older age, high SOFA score and d-dimer greater than 1 μg/mL.
Journal ArticleDOI
A pneumonia outbreak associated with a new coronavirus of probable bat origin
Peng Zhou,Xing-Lou Yang,Xian Guang Wang,Ben Hu,Lei Zhang,Wei Zhang,Hao Rui Si,Yan Zhu,Bei Li,Chao Lin Huang,Hui-Dong Chen,Jing Chen,Yun Luo,Hua Guo,Ren Di Jiang,Meiqin Liu,Ying Chen,Xu Rui Shen,Xi Wang,Xiao Shuang Zheng,Kai Zhao,Quanjiao Chen,Fei Deng,Lin Lin Liu,Bing Yan,Fa Xian Zhan,Yan-Yi Wang,Gengfu Xiao,Zhengli Shi +28 more
TL;DR: Identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China, and it is shown that this virus belongs to the species of SARSr-CoV, indicates that the virus is related to a bat coronav virus.
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