Hepatitis C virus core protein induces lipid droplet redistribution in a microtubule- and dynein-dependent manner.
Attachment of hepatitis C virus (HCV) core protein to lipid droplets (LDs) is linked to release of infectious progeny from infected cells. Core progressively coats the entire LD surface from a unique site on the organelle, and this process coincides with LD aggregation around the nucleus. We demonstrate that LD redistribution requires only core protein and is accompanied by reduced abundance of adipocyte differentiation-related protein (ADRP) on LD surfaces. Using small hairpin RNA technology, we show that knock down of ADRP has a similar phenotypic effect on LD redistribution. Hence, ADRP is crucial to maintain a disperse intracellular distribution of LDs. From additional experimental evidence, LDs are associated with microtubules and aggregate principally around the microtubule-organizing centre in HCV-infected cells. Disrupting the microtubule network or microinjecting anti-dynein antibody prevented core-mediated LD redistribution. Moreover, microtubule disruption reduced virus titres, implicating transport networks in virus assembly and release. We propose that the presence of core on LDs favours their movement towards the nucleus, possibly to increase the probability of interaction between sites of HCV RNA replication and virion assembly.
Boulant
Steeve
S
MRC Virology Unit, Institute of Virology, Church Street, Glasgow G11 5JR, UK. steeve_boulant@hms.harvard.edu
Douglas
Mark W
MW
Moody
Laura
L
Budkowska
Agata
A
Targett-Adams
Paul
P
McLauchlan
John
J
D001692:Biological Transport; D001896:Boron Compounds / Q000494:pharmacology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D004398:Dyneins / Q000737:chemistry*; D016174:Hepacivirus / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D010641:Phenotype; D034741:RNA, Small Interfering / Q000378:metabolism; D014758:Viral Core Proteins / Q000737:chemistry / Q000502:physiology*; D014771:Virion / Q000737:chemistry
C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001896:Boron Compounds; D008055:Lipids; D034741:RNA, Small Interfering; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D004398:Dyneins