The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Essential Role of Domain III of Nonstructural Protein 5A for Hepatitis C Virus Infectious Particle Assembly
Open accessAbstract
Persistent infection with the hepatitis C virus (HCV) is a major risk factor for the development of liver cirrhosis and hepatocellular carcinoma. With an estimated about 3% of the world population infected with this virus, the lack of a prophylactic vaccine and a selective therapy, chronic hepatitis C currently is a main indication for liver transplantation. The establishment of cell-based replication and virus production systems has led to first insights into the functions of HCV proteins. However, the role of nonstructural protein 5A (NS5A) in the viral replication cycle is so far not known. NS5A is a membrane-associated RNA-binding protein assumed to be involved in HCV RNA replication. Its numerous interactions with the host cell suggest that NS5A is also an important determinant for pathogenesis and persistence. In this study we show that NS5A is a key factor for the assembly of infectious HCV particles. We specifically identify the C-terminal domain III as the primary determinant in NS5A for particle formation. We show that both core and NS5A colocalize on the surface of lipid droplets, a proposed site for HCV particle assembly. Deletions in domain III of NS5A disrupting this colocalization abrogate infectious particle formation and lead to an enhanced accumulation of core protein on the surface of lipid droplets. Finally, we show that mutations in NS5A causing an assembly defect can be rescued by trans-complementation. These data provide novel insights into the production of infectious HCV and identify NS5A as a major determinant for HCV assembly. Since domain III of NS5A is one of the most variable regions in the HCV genome, the results suggest that viral isolates may differ in their level of virion production and thus in their level of fitness and pathogenesis.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
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
Production of infectious hepatitis C virus in tissue culture from a cloned viral genome
Wakita, T., Pietschmann, T., Kato, T., Date, T., Miyamoto, M., Zhao, Z., Murthy, K., Habermann, A., Kräusslich, H.-G., Mizokami, M., et al. (2005) · Nature Medicine · doi:10.1038/nm1268 · Cited by 2,754
Self-citationComplete Replication of Hepatitis C Virus in Cell Culture
Lindenbach, B. D., Evans, M. J., Syder, A. J., Wölk, B., Tellinghuisen, T. L., Liu, C. C., Maruyama, T., Hynes, R. O., Burton, D. R., McKeating, J. A., et al. (2005) · Science · doi:10.1126/science.1114016 · Cited by 2,238
Efficient Initiation of HCV RNA Replication in Cell Culture
Blight, K. J., Kolykhalov, A. A., & Rice, C. M. (2000) · Science · doi:10.1126/science.290.5498.1972 · Cited by 1,412
Replication of hepatitis C virus
Moradpour, D., Penin, F., & Rice, C. M. (2007) · Nature Reviews Microbiology · doi:10.1038/nrmicro1645 · Cited by 1,336
The lipid droplet is an important organelle for hepatitis C virus production
Miyanari, Y., Atsuzawa, K., Usuda, N., Watashi, K., Hishiki, T., Zayas, M., Bartenschlager, R., Wakita, T., Hijikata, M., & Shimotohno, K. (2007) · Nature Cell Biology · doi:10.1038/ncb1631 · Cited by 1,249
Self-citationHighly Permissive Cell Lines for Subgenomic and Genomic Hepatitis C Virus RNA Replication
Blight, K. J., McKeating, J. A., & Rice, C. M. (2002) · Journal of Virology · doi:10.1128/jvi.76.24.13001-13014.2002 · Cited by 1,193
Slot, J. W., Geuze, H. J., Gigengack, S., Lienhard, G. E., & James, D. E. (1991) · The Journal of cell biology · doi:10.1083/jcb.113.1.123 · Cited by 862
Adaptive immune responses in acute and chronic hepatitis C virus infection
Bowen, D. G., & Walker, C. M. (2005) · Nature · doi:10.1038/nature04079 · Cited by 756
Pietschmann, T., Kaul, A., Koutsoudakis, G., Shavinskaya, A., Kallis, S., Steinmann, E., Abid, K., Negro, F., Dreux, M., Cosset, F.-L., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504877103 · Cited by 730
Self-citation
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
Guedj, J., Dahari, H., Rong, L., Sansone, N. D., Nettles, R. E., Cotler, S. J., Layden, T. J., Uprichard, S. L., & Perelson, A. S. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1203110110 · Cited by 339
Viral immune modulators perturb the human molecular network by common and unique strategies
Pichlmair, A., Kandasamy, K., Alvisi, G., Mulhern, O., Sacco, R., Habjan, M., Binder, M., Stefanovic, A., Eberle, C.-A., Goncalves, A., et al. (2012) · Nature · doi:10.1038/nature11289 · Cited by 262
Self-citationAbnormalities of lipid metabolism in hepatitis C virus infection
Negro, F. (2010) · Gut · doi:10.1136/gut.2009.192732 · Cited by 162
Liu, Y., Wang, C., Mueller, S., Paul, A. V., Wimmer, E., & Jiang, P. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1001066 · Cited by 142
Metadata
- Authors
- Appel, N., Zayas, M., Miller, S., Krijnse-Locker, J., Schaller, T., Friebe, P., Kallis, S., Engel, U., & Bartenschlager, R.
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2008-03-28
- Volume
- 4
- Issue
- 3
- Pages
- e1000035
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- OpenAlex
- W2075557556
- Cited by
- 466
- References
- 46
- FWCI
- 28.79
- Type
- journal article
- Language
- en
- Open access
- gold
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Essential Role of Domain III of Nonstructural Protein 5A for Hepatitis C Virus Infectious Particle Assembly. https://app.cochat.ai/papers/10.1371/journal.ppat.1000035
- The paper
- Appel, N., Zayas, M., Miller, S., Krijnse-Locker, J., Schaller, T., Friebe, P., Kallis, S., Engel, U., & Bartenschlager, R. (2008). Essential Role of Domain III of Nonstructural Protein 5A for Hepatitis C Virus Infectious Particle Assembly. PLoS Pathogens. https://doi.org/10.1371/journal.ppat.1000035
Data sources
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.
