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Recruitment and Activation of a Lipid Kinase by Hepatitis C Virus NS5A Is Essential for Integrity of the Membranous Replication Compartment
Open accessAbstract
SUMMARY Hepatitis C virus (HCV) is a major causative agent of chronic liver disease in humans. To gain insight into host factor requirements for HCV replication we performed a siRNA screen of the human kinome and identified 13 different kinases, including phosphatidylinositol-4 kinase III alpha (PI4KIIIα) as required for HCV replication. Consistent with elevated levels of the PI4KIIIα product phosphatidylinositol-4-phosphate (PI4P) detected in HCV infected cultured hepatocytes and liver tissue from chronic hepatitis C patients, the enzymatic activity of PI4KIIIα was critical for HCV replication. Viral nonstructural protein 5A (NS5A) was found to interact with PI4KIIIα and stimulate its kinase activity. The absence of PI4KIIIα activity induced a dramatic change in the ultrastructural morphology of the membranous HCV replication complex. Our analysis suggests that the direct activation of a lipid kinase by HCV NS5A contributes critically to the integrity of the membranous viral replication complex.
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Cited by
The HCV Life Cycle: In vitro Tissue Culture Systems and Therapeutic Targets
Gerold, G., & Pietschmann, T. (2014) · Digestive Diseases · doi:10.1159/000360830 · Cited by 4,854
Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation
Balla, T. (2013) · Physiological Reviews · doi:10.1152/physrev.00028.2012 · Cited by 1,638
Self-citationUnderstanding the hepatitis C virus life cycle paves the way for highly effective therapies
Scheel, T. K. H., & Rice, C. M. (2013) · Nature Medicine · doi:10.1038/nm.3248 · Cited by 554
A novel probe for phosphatidylinositol 4-phosphate reveals multiple pools beyond the Golgi
Hammond, G. R. V., Machner, M. P., & Balla, T. (2014) · Journal of Cell Biology · doi:10.1083/jcb.201312072 · Cited by 453
Self-citationRewiring cellular networks by members of the Flaviviridae family
Neufeldt, C. J., Cortese, M., Acosta, E. G., & Bartenschlager, R. (2018) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2017.170 · Cited by 409
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Metadata
- Authors
- Reiss, S., Rebhan, I., Backes, P., Romero-Brey, I., Erfle, H., Matula, P., Kaderali, L., Poenisch, M., Blankenburg, H., Hiet, M.-S., Longerich, T., Diehl, S., Ramirez, F., Balla, T., Rohr, K., Kaul, A., Bühler, S., Pepperkok, R., Lengauer, T., Albrecht, M., Eils, R., Schirmacher, P., Lohmann, V., & Bartenschlager, R.
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 9
- Issue
- 1
- Pages
- 32-45
- ISSN
- 1931-3128 (ISSN-L)
- OpenAlex
- W1997385930
- Cited by
- 495
- References
- 0
- FWCI
- 33.63
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: Recruitment and Activation of a Lipid Kinase by Hepatitis C Virus NS5A Is Essential for Integrity of the Membranous Replication Compartment. https://app.cochat.ai/papers/10.1016/j.chom.2010.12.002
- The paper
- Reiss, S., Rebhan, I., Backes, P., Romero-Brey, I., Erfle, H., Matula, P., Kaderali, L., Poenisch, M., Blankenburg, H., Hiet, M.-S., Longerich, T., Diehl, S., Ramirez, F., Balla, T., Rohr, K., Kaul, A., Bühler, S., Pepperkok, R., Lengauer, T., . . . Bartenschlager, R. (2011). Recruitment and Activation of a Lipid Kinase by Hepatitis C Virus NS5A Is Essential for Integrity of the Membranous Replication Compartment. Cell Host & Microbe. https://doi.org/10.1016/j.chom.2010.12.002
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
