Lipid interactions during virus entry and infection

Abstract

For entry and infection viruses have developed numerous strategies to subjugate indispensable cellular factors and functions. Host cell lipids and cellular lipid synthesis machinery are no exception. Not only do viruses exploit existing lipid signalling and modifications for virus entry and trafficking, they also reprogram lipid synthesis, metabolism, and compartmentalization for assembly and egress. Here we review these various concepts and highlight recent progress in understanding viral interactions with host cell lipids during entry and assembly.

Figure 1

Virus-mediated subjugation and modulation of host lipids during infection. The lifecycle of most viruses proceeds through a series of basic steps: binding and internalization, fusion, uncoating of the viral genome, its replication, assembly of new particles, and budding or release of the newly made viruses. A multitude of viruses have learned to take advantage of host cell lipids during each of these stages. For binding and entry viruses hijack lipid based receptors and utilize existing lipid-based signalling. They rely on host phosphatidylinositol phosphate signalling for endosomal trafficking and differential endosomal lipid composition to assure fusion occurs at the appropriate time and place. Once viral gene expression ensues, viruses express factors to subjugate intracellular membrane compartments to build replication complexes, assemble viral factories, and alter lipid metabolism. Pictured are the stages of virus infection in which interplay between viruses and host lipids occur. The various stages in the lifecycle of a virus in which cellular lipids can be altered or subjugated are pictured with example viruses listed in parentheses (see text for details). SV40 (simian virus 40); VSV (vesicular stomatitis virus); IAV (influenza A virus); VACV (vaccinia virus); HSV-1 (herpes simplex virus 1); BMP [bis(monoacylglycero)phosphate]; DENV (dengue virus); WNV (West Nile virus); HCV (hepatitis C virus); HCMV (human cytomegalovirus); HIV (human immunodeficiency virus); EE (early endosome); LE (late endosome); GM1 (GM1 ganglioside); PS (phosphatidylserine); PI3K (phosphoinositde-3 kinase).