Hepatitis C virus core protein induces lipid droplet redistribution in a microtubule- and dynein-dependent manner.
Traffic
; 9(8): 1268-82, 2008 Aug.
Article
em En
| MEDLINE
| ID: mdl-18489704
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas do Core Viral
/
Dineínas
/
Hepacivirus
/
Lipídeos
/
Microtúbulos
Limite:
Humans
Idioma:
En
Revista:
Traffic
Assunto da revista:
FISIOLOGIA
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Reino Unido