The hepatitis C virus Core protein is a potent nucleic acid chaperone that directs dimerization of the viral (+) strand RNA in vitro.
The hepatitis C virus (HCV) is an important human pathogen causing chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. HCV is an enveloped virus with a positive-sense, single-stranded RNA genome encoding a single polyprotein that is processed to generate viral proteins. Several hundred molecules of the structural Core protein are thought to coat the genome in the viral particle, as do nucleocapsid (NC) protein molecules in Retroviruses, another class of enveloped viruses containing a positive-sense RNA genome. Retroviral NC proteins also possess nucleic acid chaperone properties that play critical roles in the structural remodelling of the genome during retrovirus replication. This analogy between HCV Core and retroviral NC proteins prompted us to investigate the putative nucleic acid chaperoning properties of the HCV Core protein. Here we report that Core protein chaperones the annealing of complementary DNA and RNA sequences and the formation of the most stable duplex by strand exchange. These results show that the HCV Core is a nucleic acid chaperone similar to retroviral NC proteins. We also find that the Core protein directs dimerization of HCV (+) RNA 3' untranslated region which is promoted by a conserved palindromic sequence possibly involved at several stages of virus replication.
Cristofari
Gaël
G
LaboRetro, INSERM #412, ENS, 46, allée d'Italie, 69364 Lyon Cedex 07, France.
Ivanyi-Nagy
Roland
R
Gabus
Caroline
C
Boulant
Steeve
S
Lavergne
Jean-Pierre
JP
Penin
François
F
Darlix
Jean-Luc
JL
D020413:3' Untranslated Regions; D001483:Base Sequence; D017124:Conserved Sequence; D004279:DNA, Viral / Q000737:chemistry / Q000378:metabolism*; D019281:Dimerization; D016174:Hepacivirus / Q000235:genetics* / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization; D012367:RNA, Viral / Q000737:chemistry / Q000378:metabolism*; D014758:Viral Core Proteins / Q000378:metabolism*; D014779:Virus Replication
D020413:3' Untranslated Regions; D004279:DNA, Viral; D018832:Molecular Chaperones; D012367:RNA, Viral; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus