Nuclear factors are involved in hepatitis C virus RNA replication
Abstract
Unraveling the molecular basis of the life cycle of hepatitis C virus (HCV), a prevalent agent of human liver disease, entails the identification of cell-encoded factors that participate in the replication of the viral RNA genome. This study provides evidence that the so-called NF/NFAR proteins, namely, NF90/NFAR-1, NF110/NFAR-2, NF45, and RNA helicase A (RHA), which mostly belong to the dsRBM protein family, are involved in the HCV RNA replication process. NF/NFAR proteins were shown to specifically bind to replication signals in the HCV genomic 5′ and 3′ termini and to promote the formation of a looplike structure of the viral RNA. In cells containing replicating HCV RNA, the generally nuclear NF/NFAR proteins accumulate in the cytoplasmic viral replication complexes, and the prototype NFAR protein, NF90/NFAR-1, stably interacts with a viral protein. HCV replication was inhibited in cells where RNAi depleted RHA from the cytoplasm. Likewise, HCV replication was hindered in cells that contained another NF/NFAR protein recruiting virus. The recruitment of NF/NFAR proteins by HCV is assumed to serve two major purposes: to support 5′–3′ interactions of the viral RNA for the coordination of viral protein and RNA synthesis and to weaken host–defense mechanisms.
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Footnotes
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Reprint requests to: Sven-Erik Behrens, Institute of Biochemistry and Biotechnology, Kurt-Mothes-Strauss 3, D-06120 Halle/Saale, Germany; e-mail: Sven.Behrens{at}biochemtech.uni-halle.de; fax: +49-345-5527837.
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Article published online ahead of print. Article and publication date are at http://www.rnajournal.org/cgi/doi/10.1261/rna.594207.
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- Received April 10, 2007.
- Accepted June 27, 2007.
- Copyright © 2007 RNA Society