Phospholipid synthesis fueled by lipid droplets drives the structural development of poliovirus replication organelles

PLoS Pathogens
Ekaterina G ViktorovaGeorge A Belov

Abstract

Rapid development of complex membranous replication structures is a hallmark of picornavirus infections. However, neither the mechanisms underlying such dramatic reorganization of the cellular membrane architecture, nor the specific role of these membranes in the viral life cycle are sufficiently understood. Here we demonstrate that the cellular enzyme CCTα, responsible for the rate-limiting step in phosphatidylcholine synthesis, translocates from the nuclei to the cytoplasm upon infection and associates with the replication membranes, resulting in the rerouting of lipid synthesis from predominantly neutral lipids to phospholipids. The bulk supply of long chain fatty acids necessary to support the activated phospholipid synthesis in infected cells is provided by the hydrolysis of neutral lipids stored in lipid droplets. Such activation of phospholipid synthesis drives the massive membrane remodeling in infected cells. We also show that complex membranous scaffold of replication organelles is not essential for viral RNA replication but is required for protection of virus propagation from the cellular anti-viral response, especially during multi-cycle replication conditions. Inhibition of infection-specific phospholipid synthesis...Continue Reading

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Citations

May 24, 2019·Journal of Leukocyte Biology·Filipe S Pereira-DutraPatrícia T Bozza
Jan 7, 2020·The American Journal of Chinese Medicine·Meng-Jie WangYuan-Yuan Liu
Oct 1, 2019·Annual Review of Virology·Ellen Ketter, Glenn Randall
Mar 14, 2019·Frontiers in Microbiology·Zhenlu ZhangXiaofeng Wang
Sep 26, 2020·Frontiers in Microbiology·Xinhong LiXiaoyue Chen
Jan 28, 2021·Viruses·Christine E Peters, Jan E Carette
Feb 7, 2021·Trends in Cell Biology·Eva HerkerMaria Bohnert
Feb 3, 2021·Viruses·Georg Wolff, Montserrat Bárcena
Sep 9, 2020·Chemistry and Physics of Lipids·Christelle F AncajasMichael D Best
Apr 4, 2021·Viruses·Terry Jackson, Graham J Belsham
Apr 6, 2021·Frontiers in Cell and Developmental Biology·Louise H WongEmily R Eden

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Methods Mentioned

BETA
electron microscopy
GTPases
co-IP
co-immunoprecipitation assay
immunoprecipitation
transfections
transfection
PCR

Software Mentioned

Click
GraphPad Prizm
ImageJ
it
Image Studio

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