Lipid Droplets and Viral Infections - Methods in Cell Biology - page 165

Viruses that localize to LDs
The lifecycle of HCV, a member of the Flaviridae family, is intimately tied to the
lipid metabolism of its host cell: (1) HCV circulates in the blood as a lipoviroparticle
rich in cholesterol esters and containing apolipoproteins, such as apoE and apoB
( Andre et al., 2002; Nielsen et al., 2006, 2008; Thomssen et al., 1992 ); (2) entry
of HCV depends on specific receptors, including the low-density lipoprotein
(LDL) receptor and the scavenger receptor class-B/type-I, both of which are
involved in lipoprotein uptake ( Sabahi, 2009 ); (3) viral RNA replication induces
extensive membrane alterations and the formation of vesicular structures that exhibit
many characteristics of lipid rafts ( Aizaki et al., 2004; Shi et al., 2003 ); (4) HCV
assembly requires localization of some HCV proteins to host LDs ( Miyanari
et al., 2007 ), and the release of progeny virions is strongly associated with the very
low density lipoprotein (VLDL) secretion pathway ( Chang et al., 2007; Gastaminza
et al., 2008; Huang et al., 2007 ).
Although the detailed role of LDs in viral assembly and egress is unknown,
two HCV proteins, the nucleocapsid core and regulatory protein NS5A, are translo-
cated from the endoplasmic reticulum (ER) onto LDs through the actions of the host
protein diacylglycerol acetyltransferase-1 (DGAT1), one of two triglyceride-
synthesizing enzymes ( Camus et al., 2013; Herker et al., 2010 )( Fig. 10.2 A). Inhibi-
tion of DGAT1 activity through protein depletion or pharmacological inhibition
FIGURE 10.2
Role of DGAT1 in HCV proteins interaction with lipid droplets. (A) Model of DGAT1-
mediated loading of the HCV core and NS5A proteins onto LDs. (B) Core stabilizes
DGAT1-generated LDs and causes steatosis.