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Journal of Virology, December 2008, p. 12082-12093, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01405-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

RNA-Binding Protein hnRNP D Modulates Internal Ribosome Entry Site-Dependent Translation of Hepatitis C Virus RNA{triangledown}

Ki Young Paek, Chon Saeng Kim, Sung Mi Park, Jong Heon Kim, and Sung Key Jang*

POSTECH Biotech Center, Department of Life Science, Pohang University of Science and Technology, San 31, Hyoja Dong, Pohang, Kyungbuk 790-784, Republic of Korea

Received 1 July 2008/ Accepted 25 September 2008

Hepatitis C virus (HCV) is one of the major causative agents of virus-related hepatitis, liver cirrhosis, and hepatocellular carcinoma in humans. Translation of the HCV polyprotein is mediated by an internal ribosomal entry site (IRES) in the 5' nontranslated region of the genome. Here, we report that a cellular protein, hnRNP D, interacts with the 5' border of HCV IRES (stem-loop II) and promotes translation of HCV mRNA. Overexpression of hnRNP D in mammalian cells enhances HCV IRES-dependent translation, whereas knockdown of hnRNP D with small interfering RNAs (siRNAs) inhibits translation. In addition, sequestration of hnRNP D with an interacting DNA oligomer inhibits the translation of HCV mRNA in an in vitro system. Ribosome profiling experiments reveal that HCV RNA is redistributed from heavy to light polysome fractions upon suppression of the hnRNP D level using specific siRNA. These results collectively suggest that hnRNP D plays an important role in the translation of HCV mRNA through interactions with the IRES. Moreover, knockdown of hnRNP D with siRNA significantly hampers infection by HCV. A potential role of hnRNP D in HCV proliferation is discussed.

* Corresponding author. Mailing address: PBC, Department of Life Science, Pohang University of Science and Technology, San 31, Hyoja Dong, Pohang, Kyungbuk 790-784, Republic of Korea. Phone: 82-54-279-2298. Fax: 82-54-279-8009. E-mail: sungkey{at}postech.ac.kr

{triangledown} Published ahead of print on 8 October 2008.

Journal of Virology, December 2008, p. 12082-12093, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01405-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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