The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
Viral and therapeutic control of IFN-β promoter stimulator 1 during hepatitis C virus infection
Abstract
Viral signaling through retinoic acid-inducible gene-I (RIG-I) and its adaptor protein, IFN promoter-stimulator 1 (IPS-1), activates IFN regulatory factor-3 (IRF-3) and the host IFN-α/β response that limits virus infection. The hepatitis C virus (HCV) NS3/4A protease cleaves IPS-1 to block RIG-I signaling, but how this regulation controls the host response to HCV is not known. Moreover, endogenous IPS-1 cleavage has not been demonstrated in the context of HCV infection in vitro or in vivo . Here, we show that HCV infection transiently induces RIG-I- and IPS-1-dependent IRF-3 activation. This host response limits HCV production and constrains cellular permissiveness to infection. However, HCV disrupts this response early in infection by NS3/4A cleavage of IPS-1 at C508, releasing IPS-1 from the mitochondrial membrane. Cleavage results in subcellular redistribution of IPS-1 and loss of interaction with RIG-I, thereby preventing downstream activation of IRF-3 and IFN-β induction. Liver tissues from chronically infected patients similarly demonstrate subcellular redistribution of IPS-1 in infected hepatocytes and IPS-1 cleavage associated with a lack of ISG15 expression and conjugation of target proteins in vivo . Importantly, small-molecule inhibitors of NS3/4A prevent cleavage and restore RIG-I signaling of IFN-β induction. Our results suggest a dynamic model in which early activation of IRF-3 and induction of antiviral genes are reversed by IPS-1 proteolysis and abrogation of RIG-I signaling as NS3/4A accumulates in newly infected cells. HCV protease inhibitors effectively prevent IPS-1 proteolysis, suggesting they may be capable of restoring this innate host response in clinical practice.
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
Yoneyama, M., Kikuchi, M., Natsukawa, T., Shinobu, N., Imaizumi, T., Miyagishi, M., Taira, K., Akira, S., & Fujita, T. (2004) · Nature Immunology · doi:10.1038/ni1087 · Cited by 3,929
Self-citationSeth, R. B., Sun, L., Ea, C.-K., & Chen, Z. J. (2005) · Cell · doi:10.1016/j.cell.2005.08.012 · Cited by 3,329
Global epidemiology of hepatitis C virus infection
Shepard, C. W., Finelli, L., & Alter, M. J. (2005) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(05)70216-4 · Cited by 2,758
IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction
Kawai, T., Takahashi, K., Sato, S., Coban, C., Kumar, H., Kato, H., Ishii, K. J., Takeuchi, O., & Akira, S. (2005) · Nature Immunology · doi:10.1038/ni1243 · Cited by 2,562
Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus
Meylan, E., Curran, J., Hofmann, K., Moradpour, D., Binder, M., Bartenschlager, R., & Tschopp, J. (2005) · Nature · doi:10.1038/nature04193 · Cited by 2,401
VISA Is an Adapter Protein Required for Virus-Triggered IFN-β Signaling
Xu, L.-G., Wang, Y.-Y., Han, K.-J., Li, L.-Y., Zhai, Z., & Shu, H.-B. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.08.014 · Cited by 1,853
Robust hepatitis C virus infection in vitro
Zhong, J., Gastaminza, P., Cheng, G., Kapadia, S., Kato, T., Burton, D. R., Wieland, S. F., Uprichard, S. L., Wakita, T., & Chisari, F. V. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503596102 · Cited by 1,709
Yoneyama, M., Kikuchi, M., Matsumoto, K., Imaizumi, T., Miyagishi, M., Taira, K., Foy, E., Loo, Y.-M., Gale, M., Akira, S., et al. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.5.2851 · Cited by 1,689
Self-citationCell Type-Specific Involvement of RIG-I in Antiviral Response
Kato, H., Sato, S., Yoneyama, M., Yamamoto, M., Uematsu, S., Matsui, K., Tsujimura, T., Takeda, K., Fujita, T., Takeuchi, O., et al. (2005) · Immunity · doi:10.1016/j.immuni.2005.04.010 · Cited by 1,368
Self-citationSato, M., Suemori, H., Hata, N., Asagiri, M., Ogasawara, K., Nakao, K., Nakaya, T., Katsuki, M., Noguchi, S., Tanaka, N., et al. (2000) · Immunity · doi:10.1016/s1074-7613(00)00053-4 · Cited by 1,339
Cited by
Repertoires of Autophagy in the Pathogenesis of Ocular Diseases
Li, Y.-J., Jiang, Q., Cao, G.-F., Yao, J., & Yan, B. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373980 · Cited by 16,304
Distinct RIG-I and MDA5 Signaling by RNA Viruses in Innate Immunity
Loo, Y.-M., Fornek, J., Crochet, N., Bajwa, G., Perwitasari, O., Martinez-Sobrido, L., Akira, S., Gill, M. A., García-Sastre, A., Katze, M. G., et al. (2008) · Journal of Virology · doi:10.1128/jvi.01080-07 · Cited by 1,071
Self-citationToll‐like Receptor and RIG‐1‐like Receptor Signaling
Kawai, T., & Akira, S. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1443.020 · Cited by 986
Viral evasion and subversion of pattern-recognition receptor signalling
Bowie, A. G., & Unterholzner, L. (2008) · Nature Reviews Immunology · doi:10.1038/nri2436 · Cited by 746
Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2
Saito, T., Hirai, R., Loo, Y.-M., Owen, D., Johnson, C. L., Sinha, S. C., Akira, S., Fujita, T., & Gale, M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0606699104 · Cited by 744
Self-citation
Metadata
- Authors
- Loo, Y.-M., Owen, D. M., Li, K., Erickson, A. K., Johnson, C. L., Fish, P. M., Carney, D. S., Wang, T., Ishida, H., Yoneyama, M., Fujita, T., Saito, T., Lee, W. M., Hagedorn, C. H., Lau, D. T.-Y., Weinman, S. A., Lemon, S. M., & Gale, M.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2006-04-11
- Volume
- 103
- Issue
- 15
- Pages
- 6001-6006
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2147727360
- Cited by
- 391
- References
- 25
- FWCI
- 15.58
- Type
- journal article
- Language
- en
- Open access
- closed
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: Viral and therapeutic control of IFN-β promoter stimulator 1 during hepatitis C virus infection. https://app.cochat.ai/papers/10.1073/pnas.0601523103
- The paper
- Loo, Y.-M., Owen, D. M., Li, K., Erickson, A. K., Johnson, C. L., Fish, P. M., Carney, D. S., Wang, T., Ishida, H., Yoneyama, M., Fujita, T., Saito, T., Lee, W. M., Hagedorn, C. H., Lau, D. T.-Y., Weinman, S. A., Lemon, S. M., & Gale, M. (2006). Viral and therapeutic control of IFN-β promoter stimulator 1 during hepatitis C virus infection. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0601523103
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.
