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Journal of Virology, April 2007, p. 3852-3865, Vol. 81, No. 8
0022-538X/07/$08.00+0     doi:10.1128/JVI.01311-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

An RNA-Binding Protein, hnRNP A1, and a Scaffold Protein, Septin 6, Facilitate Hepatitis C Virus Replication{triangledown}

Chon Saeng Kim,1 Su Kyoung Seol,1 Ok-Kyu Song,2 Ji Hoon Park,1 and Sung Key Jang1*

PBC, Department of Life Science, Pohang University of Science and Technology, Pohang, Kyungbuk 790-784, Republic of Korea,1 Panbionet Corp., Pohang, Kyungbuk, Republic of Korea2

Received 22 June 2006/ Accepted 7 January 2007

Hepatitis C virus (HCV) is a positive-sense single-stranded RNA virus. NS5b is an RNA-dependent RNA polymerase that polymerizes the newly synthesized RNA. HCV likely uses host proteins for its replication, similar to other RNA viruses. To identify the cellular factors involved in HCV replication, we searched for cellular proteins that interact with the NS5b protein. HnRNP A1 and septin 6 proteins were identified by coimmunoprecipitation and yeast two-hybrid screening, respectively. Interestingly, septin 6 protein also interacts with hnRNP A1. Moreover, hnRNP A1 interacts with the 5'-nontranslated region (5' NTR) and the 3' NTR of HCV RNA containing the cis-acting elements required for replication. Knockdown of hnRNP A1 and overexpression of C-terminally truncated hnRNP A1 reduced HCV replication. In addition, knockdown of septin 6 and overexpression of N-terminally truncated septin 6 inhibited HCV replication. These results indicate that the host proteins hnRNP A1 and septin 6 play important roles in the replication of HCV through RNA-protein and protein-protein interactions.

* Corresponding author. Mailing address: PBC, Department of Life Science, Pohang University of Science and Technology, San 31, Hyoja-Dong, Pohang 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 17 January 2007.

Journal of Virology, April 2007, p. 3852-3865, Vol. 81, No. 8
0022-538X/07/$08.00+0     doi:10.1128/JVI.01311-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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