Host Lipids in Positive-Strand RNA Virus Genome Replication.

Zhenlu Zhang,Guijuan He,Glenn Randall,Natalie A Filipowicz,Xiaofeng Wang,Benjamin G Kopek,George A Belov

doi:10.3389/fmicb.2019.00286

Abstract

Membrane association is a hallmark of the genome replication of positive-strand RNA viruses [(+)RNA viruses]. All well-studied (+)RNA viruses remodel host membranes and lipid metabolism through orchestrated virus-host interactions to create a suitable microenvironment to survive and thrive in host cells. Recent research has shown that host lipids, as major components of cellular membranes, play key roles in the replication of multiple (+)RNA viruses. This review focuses on how (+)RNA viruses manipulate host lipid synthesis and metabolism to facilitate their genomic RNA replication, and how interference with the cellular lipid metabolism affects viral replication.

Highlights

Lipids are a diverse group of amphipathic or non-polar molecules essential for all cellular life forms
In the classification system proposed by the lipid metabolites and pathways strategy (LIPID MAPS), lipids are classified into eight categories based on ketoacyl and isoprene groups: glycerophospholipids, sphingolipids, sterol lipids, fatty acids (FAs), glycerolipids, saccharolipids, polyketides, and prenol lipids (Fahy et al, 2011)
Some lipids are stored in lipid droplets (LDs) to serve as energy sources, e.g., triacylglycerol (TAG) and steryl ester (StE) that are produced from free FAs and sterols, respectively (Zweytick et al, 2000; Klug and Daum, 2014)

Summary

INTRODUCTION

Lipids are a diverse group of amphipathic or non-polar molecules essential for all cellular life forms. One key feature conserved among (+)RNA viruses of eukaryotes is that RNA genome synthesis occurs in tight association with remodeled organelle membranes (Figure 2 and Table 1), such as mitochondria (Rubino and Russo, 1998; Miller et al, 2001), chloroplast (Prod’homme et al, 2001), endosome (Grimley et al, 1968; Froshauer et al, 1988), peroxisome (Rubino and Russo, 1998; McCartney et al, 2005; Panavas et al, 2005; Pathak et al, 2008), or endoplasmic reticulum (ER) (Restrepo-Hartwig and Ahlquist, 1996, 1999; Suhy et al, 2000; Gosert et al, 2003) It is not well understood why viruses replicate in association with specific organellar membranes, differences in membrane lipid (Figure 3) (van Meer et al, 2008) and protein composition should play a critical role. PC is produced from either the Kennedy pathway or the CDP-DAG (cytidine diphosphate-diacylglyerol)

Mitochondrial membrane PE

Phosphatidylinositol Derivatives

Findings

Phosphatidic Acid