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LIPID DROPLETS FUEL SARS-COV-2 REPLICATION AND PRODUCTION OF INFLAMMATORY MEDIATORS
SARS-CoV-2
Replicação
Produção
Mediadores inflamatórios
Rede Genômica Fiocruz
GENOMAHCOV
Author
Affilliation
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.
Keywords in Portuguese
Gotículas lipídicasSARS-CoV-2
Replicação
Produção
Mediadores inflamatórios
Rede Genômica Fiocruz
GENOMAHCOV
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