Hepatitis C virus core protein acts as a trans-modulating factor on internal translation initiation of the viral RNA.

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Citation

Boni S, Lavergne JP, Boulant S, Cahour A

Hepatitis C virus core protein acts as a trans-modulating factor on internal translation initiation of the viral RNA.

J Biol Chem. 2005 May 6;280(18):17737-48. Epub 2005 Mar 9.

PubMed ID
15760888 [ View in PubMed
]
Abstract

Translation initiation of hepatitis C virus (HCV) RNA occurs through an internal ribosome entry site (IRES) located at its 5' end. As a positive-stranded virus, HCV uses the genomic RNA template for translation and replication, but the transition between these two processes remains poorly understood. HCV core protein (HCV-C) has been proposed as a good candidate to modulate such a regulation. However, current data are still the subject of controversy in attributing any potential role in HCV translation to the HCV core protein. Here we demonstrate that HCV-C displays binding activities toward both HCV IRES and the 40 S ribosomal subunit by using centrifugation on sucrose gradients. To gain further insight into these interactions, we investigated the effect of exogenous addition of purified HCV-C on HCV IRES activity by using an in vitro reporter assay. We found that HCV IRES-mediated translation was specifically modulated by HCV-C provided in trans, in a dose-dependent manner, with up to a 5-fold stimulation of the IRES efficiency upon addition of low amounts of HCV-C, followed by a decrease at high doses. Interestingly, mutations within some domains of the IRES as well as the presence of an upstream reporter gene both lead to changes in the expected effects, consistent with the high dependence of HCV IRES function on its overall structure. Collectively, these results indicate that the HCV core protein is involved in a tight modulation of HCV translation initiation, depending on its concentration, and they suggest an important biological role of this protein in viral gene expression.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Genome polyproteinP26662Details