In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 16, No. 12 ( 2020-12-16), p. e1009127-
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.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009127
DOI:
10.1371/journal.ppat.1009127.g001
DOI:
10.1371/journal.ppat.1009127.g002
DOI:
10.1371/journal.ppat.1009127.g003
DOI:
10.1371/journal.ppat.1009127.g004
DOI:
10.1371/journal.ppat.1009127.g005
DOI:
10.1371/journal.ppat.1009127.s001
DOI:
10.1371/journal.ppat.1009127.s002
DOI:
10.1371/journal.ppat.1009127.s003
DOI:
10.1371/journal.ppat.1009127.r001
DOI:
10.1371/journal.ppat.1009127.r002
DOI:
10.1371/journal.ppat.1009127.r003
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2020
detail.hit.zdb_id:
2205412-1
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