ArticlePloS one2010
SH2 modified STAT1 induces HLA-I expression and improves IFN-γ signaling in IFN-α resistant HCV replicon cells.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 12 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 14 citations in OpenAlex.
- Unlocking therapeutic potential in traumatic brain injury: exploring microenvironmental targets, signaling pathways and translational hurdles.Inflammopharmacology · 2025Review
- Retraction: SH2 Modified STAT1 Induces HLA-I Expression and Improves IFN-γ Signaling in IFN-α Resistant HCV Replicon Cells.PloS one · 2024Article
- Temporal regulation of interferon signalling in human EndoC-βH1 cells.Journal of molecular endocrinology · 2022Article
- Expression of Concern: SH2 Modified STAT1 Induces HLA-I Expression and Improves IFN-γ Signaling in IFN-α Resistant HCV Replicon Cells.PloS one · 2022Article
- Role of STAT1 in the resistance of HBV to IFN-α.Experimental and therapeutic medicine · 2021Article
- BMX-ARHGAP fusion protein maintains the tumorigenicity of gastric cancer stem cells by activating the JAK/STAT3 signaling pathway.Cancer cell international · 2019Article
- Prostate cancer health disparities: An immuno-biological perspective.Cancer letters · 2018Article
- Hepatitis C Virus Infection Induces Autophagy as a Prosurvival Mechanism to Alleviate Hepatic ER-Stress Response.Viruses · 2016Review
- STAT1 modification improves therapeutic effects of interferons on lung cancer cells.Journal of translational medicine · 2015Article
- Suppression of interferon lambda signaling by SOCS-1 results in their excessive production during influenza virus infection.PLoS pathogens · 2014Article
- HCV infection selectively impairs type I but not type III IFN signaling.The American journal of pathology · 2014Article
- Ubiquitination-mediated regulation of interferon responses.Growth factors (Chur, Switzerland) · 2012Review
Corrections and comments
- Retraction · 2024-11-05Concerns/Issues about Data · Concerns/Issues about Image · Duplication of/in Image · Euphemisms for Duplication · Investigation by Journal/Publisher · Original Data and/or Images not Provided and/or not Available · Unreliable Results and/or Conclusions · Upgrade/Update of Prior Notice(s) ·
- Expression of concern · 2022-03-31Concerns/Issues about Data · Concerns/Issues about Image · Duplication of/in Image · Updated to Retraction ·
- Expression of concern
- Retracted
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundWe have developed multiple stable cell lines containing subgenomic HCV RNA that are resistant to treatment with interferon alpha (IFN-α. Characterization of these IFN-α resistant replicon cells showed defects in the phosphorylation and nuclear translocation of STAT1 and STAT2 proteins due to a defective Jak-STAT pathway. METHODOLOGY/PRINCIPAL
findingsIn this study, we have developed an alternative strategy to overcome interferon resistance in a cell culture model by improving intracellular STAT1 signaling. An engineered STAT1-CC molecule with double cysteine substitutions in the Src-homology 2 (SH2) domains of STAT1 (at Ala-656 and Asn-658) efficiently phosphorylates and translocates to the nucleus of IFN-resistant cells in an IFN-γ dependent manner. Transfection of a plasmid clone containing STAT1-CC significantly activated the GAS promoter compared to wild type STAT1 and STAT3. The activity of the engineered STAT1-CC is dependent upon the phosphorylation of tyrosine residue 701, since the construct with a substituted phenylalanine residue at position 701 (STAT1-CC-Y701F) failed to activate GAS promoter in the replicon cells. Intracellular expression of STAT1-CC protein showed phosphorylation and nuclear translocation in the resistant cell line after IFN-γ treatment. Transient transfection of STAT1-CC plasmid clone into an interferon resistant cell line resulted in inhibition of viral replication and viral clearance in an IFN-γ dependent manner. Furthermore, the resistant replicon cells transfected with STAT1-CC constructs significantly up regulated surface HLA-1 expression when compared to the wild type and Y to F mutant controls.
conclusionsThese results suggest that modification of the SH2 domain of the STAT1 molecule allows for improved IFN-γ signaling through increased STAT1 phosphorylation, nuclear translocation, HLA-1 surface expression, and prolonged interferon antiviral gene activation.
Indexed as
Identifiers
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.