DOI: 10.1002/hep.21608. Identification of host genes involved in hepatitis C virus replication by small interfering RNA technology

Identification of host genes involved in hepatitis C virus replication by small interfering RNA technology

10.1002/hep.21608

Crossref journal-article

Ovid Technologies (Wolters Kluwer Health)

Hepatology (276)

Abstract

Hepatitis C virus (HCV) replication is highly dependent on host cell factors. Identification of these host factors not only facilitates understanding of the biology of HCV infection but also enables the discovery of novel targets for anti-HCV therapy. To identify host genes important for HCV RNA replication, we screened a library of small interfering RNA (siRNA) that targets approximately 4,000 human genes in Huh7-derived EN5-3 cells harboring an HCV subgenomic replicon with the nonstructural region NS3-NS5B from the 1b-N strain. Nine cellular genes that potentially regulate HCV replication were identified in this screen. Silencing of these genes resulted in inhibition of HCV replication by more than 60% and exhibited minimal toxicity. Knockdown of host gene expression by these siRNAs was confirmed at the RNA level and, in some instances, at the protein level. The level of siRNA silencing of these host genes correlated well with inhibition of HCV. These genes included those that encoded a G-protein coupled receptor ( TBXA2R ), a membrane protein ( LTβ ), an adapter protein ( TRAF2 ), 2 transcription factors ( RelA and NFκB2 ), 2 protein kinases ( MKK7 and SNARK ), and 2 closely related transporter proteins ( SLC12A4 and SLC12A5 ). Of interest, some of these genes are members of the tumor necrosis factor/lymphotoxin signaling pathway. Conclusion: Findings of this study may provide important information for understanding HCV replication. In addition, these cellular genes may constitute a novel set of targets for HCV antiviral therapy. (Hepatology 2007.)

Bibliography

Ng, T. I., Mo, H., Pilot-Matias, T., He, Y., Koev, G., Krishnan, P., Mondal, R., Pithawalla, R., He, W., Dekhtyar, T., Packer, J., Schurdak, M., & Molla, A. (2007). Identification of host genes involved in hepatitis C virus replication by small interfering RNA technology. Hepatology, 45(6), 1413â1421.

Authors 13

Teresa I. Ng (first)
Hongmei Mo (additional)
Tami Pilot-Matias (additional)
Yupeng He (additional)
Gennadiy Koev (additional)
Preethi Krishnan (additional)
Rubina Mondal (additional)
Ron Pithawalla (additional)
Wenping He (additional)
Tanya Dekhtyar (additional)
Jeremy Packer (additional)
Mark Schurdak (additional)
Akhteruzzaman Molla (additional)

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Dates

Type	When
Created	18 years, 3 months ago (May 23, 2007, 8:18 p.m.)
Deposited	8 months, 3 weeks ago (Dec. 1, 2024, 7:20 a.m.)
Indexed	4 months, 2 weeks ago (April 11, 2025, 2:28 a.m.)
Issued	18 years, 2 months ago (June 1, 2007)
Published	18 years, 2 months ago (June 1, 2007)
Published Print	18 years, 2 months ago (June 1, 2007)

Funders 0

None

BibTeX

@article{Ng_2007, title={Identification of host genes involved in hepatitis C virus replication by small interfering RNA technology}, volume={45}, ISSN={0270-9139}, url={http://dx.doi.org/10.1002/hep.21608}, DOI={10.1002/hep.21608}, number={6}, journal={Hepatology}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Ng, Teresa I. and Mo, Hongmei and Pilot-Matias, Tami and He, Yupeng and Koev, Gennadiy and Krishnan, Preethi and Mondal, Rubina and Pithawalla, Ron and He, Wenping and Dekhtyar, Tanya and Packer, Jeremy and Schurdak, Mark and Molla, Akhteruzzaman}, year={2007}, month=jun, pages={1413–1421} }

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  "abstract": "<jats:sec>\n            <jats:title/>\n            <jats:p>\n                                 <jats:bold>Hepatitis C virus (HCV) replication is highly dependent on host cell factors. Identification of these host factors not only facilitates understanding of the biology of HCV infection but also enables the discovery of novel targets for anti-HCV therapy. To identify host genes important for HCV RNA replication, we screened a library of small interfering RNA (siRNA) that targets approximately 4,000 human genes in Huh7-derived EN5-3 cells harboring an HCV subgenomic replicon with the nonstructural region NS3-NS5B from the 1b-N strain. Nine cellular genes that potentially regulate HCV replication were identified in this screen. Silencing of these genes resulted in inhibition of HCV replication by more than 60% and exhibited minimal toxicity. Knockdown of host gene expression by these siRNAs was confirmed at the RNA level and, in some instances, at the protein level. The level of siRNA silencing of these host genes correlated well with inhibition of HCV. These genes included those that encoded a G-protein coupled receptor (</jats:bold>\n                                 <jats:bold>\n                                    TBXA2R\n                                 </jats:bold>\n                                 <jats:bold>), a membrane protein (</jats:bold>\n                                 <jats:bold>\n                                    LT\u03b2\n                                 </jats:bold>\n                                 <jats:bold>), an adapter protein (</jats:bold>\n                                 <jats:bold>\n                                    TRAF2\n                                 </jats:bold>\n                                 <jats:bold>), 2 transcription factors (</jats:bold>\n                                 <jats:bold>\n                                    RelA\n                                 </jats:bold>\n                                 <jats:bold>and</jats:bold>\n                                 <jats:bold>\n                                    NF\u03baB2\n                                 </jats:bold>\n                                 <jats:bold>), 2 protein kinases (</jats:bold>\n                                 <jats:bold>\n                                    MKK7\n                                 </jats:bold>\n                                 <jats:bold>and</jats:bold>\n                                 <jats:bold>\n                                    SNARK\n                                 </jats:bold>\n                                 <jats:bold>), and 2 closely related transporter proteins (</jats:bold>\n                                 <jats:bold>\n                                    SLC12A4\n                                 </jats:bold>\n                                 <jats:bold>and</jats:bold>\n                                 <jats:bold>\n                                    SLC12A5\n                                 </jats:bold>\n                                 <jats:bold>). Of interest, some of these genes are members of the tumor necrosis factor/lymphotoxin signaling pathway.</jats:bold>\n                                 <jats:bold>\n                                    Conclusion:\n                                 </jats:bold>\n                                 <jats:bold>Findings of this study may provide important information for understanding HCV replication. In addition, these cellular genes may constitute a novel set of targets for HCV antiviral therapy. (Hepatology 2007.)</jats:bold>\n                              </jats:p>\n          </jats:sec>",
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