ArticleJournal of hepatology2010
Hepatitis C virus NS2 protein triggers endoplasmic reticulum stress and suppresses its own viral replication.
Article in Journal of hepatology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 49 citations in OpenAlex.
- An evolutionarily conserved ubiquitin ligase drives infection and transmission of flaviviruses.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Role of hepcidin upregulation and proteolytic cleavage of ferroportin 1 in hepatitis C virus-induced iron accumulation.PLoS pathogens · 2023Article
- Review
- Intrinsic features of Zika Virus non-structural proteins NS2A and NS4A in the regulation of viral replication.PLoS neglected tropical diseases · 2022Article
- Endoplasmic reticulum stress in the acute intestinal epithelial injury of necrotizing enterocolitis.Pediatric surgery international · 2021Review
- Hepatitis C: From inflammatory pathogenesis to anti-inflammatory/hepatoprotective therapy.World journal of gastroenterology · 2018Review
- Article
- The Molecular Chaperone GRP78 Contributes to Toll-like Receptor 3-mediated Innate Immune Response to Hepatitis C Virus in Hepatocytes.The Journal of biological chemistry · 2016Article
- Netrin-1 Protects Hepatocytes Against Cell Death Through Sustained Translation During the Unfolded Protein Response.Cellular and molecular gastroenterology and hepatology · 2016Article
- Significance of hepatitis virus infection in the oncogenic initiation of hepatocellular carcinoma.World journal of gastroenterology · 2016Review
- Chaperones in hepatitis C virus infection.World journal of hepatology · 2016Review
- The expanding roles of endoplasmic reticulum stress in virus replication and pathogenesis.Critical reviews in microbiology · 2015Review
- Constant up-regulation of BiP/GRP78 expression prevents virus-induced apoptosis in BHK-21 cells with Japanese encephalitis virus persistent infection.Virology journal · 2015Article
- Article
- Article
- ER stress, autophagy, and RNA viruses.Frontiers in microbiology · 2014Review
- Unfolded protein response in hepatitis C virus infection.Frontiers in microbiology · 2014Review
- Hepatitis C virus and cellular stress response: implications to molecular pathogenesis of liver diseases.Viruses · 2012Review
- Activation status of integrated stress response pathways in neurones and astrocytes of HIV-associated neurocognitive disorders (HAND) cortex.Neuropathology and applied neurobiology · 2012Article
- Endoplasmic reticulum stress: its role in disease and novel prospects for therapy.Scientifica · 2012Review
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsWe previously reported that the NS2 protein of hepatitis C virus (HCV) inhibits the expression of reporter genes driven by a variety of cellular and viral promoters. The aim of the study was to determine whether the broad transcriptional repression is caused by endoplasmic reticulum (ER) stress.
methodsPhosphorylation of the translation initiation factor eIF2α and HCV replication was detected by Western and Northern blot, respectively. De novo protein synthesis was measured by metabolic labeling. Activation of ER stress responsive genes was determined by promoter reporter assay, as well as mRNA and protein measurement by real time PCR and Western blot.
resultsTransient or inducible NS2 protein expression increased eIF2α phosphorylation and reduced de novo protein synthesis. It up-regulated promoter activities and transcript levels of ER stress inducible genes including GRP78, ATF6, and GADD153, as well as GRP78 protein level. The same effect was observed when NS2 was synthesized as part of the core-E1-E2-p7-NS2 polypeptide. NS2 protein also inhibited reporter gene expression from the HCV internal ribosome entry site and consequently reduced HCV replication. The full-length HCV replicon activated GRP78, ATF6, and GADD153 promoters more efficiently than the subgenomic replicon lacking the coding sequence for both the structural proteins and NS2. Abrogation of HCV infection/replication, by an inhibitor of the NS3 protease, relieved ER stress.
conclusionsHCV infection can induce ER stress, with NS2 protein being a major mediator. The stress can be relieved by a feedback mechanism.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.