ArticleJournal of virology2008
A new role for ns polyprotein cleavage in Sindbis virus replication.
Article in Journal of virology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 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
62 citing papers in PubMed, 78 citations in OpenAlex.
- The pathogenicity and virulence of Sindbis virus.Virulence · 2026Review
- Chikungunya virus nsP2: Insights into viral replication, pathogenesis, and therapeutic targeting.Virulence · 2026Review
- Alphavirus replicase and regulatory RNA elements in host interactions and viral vector engineering.Journal of virology · 2026Review
- Antagonism of RNA silencing in the yellow fever mosquito,Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Trans-complementation of chikungunya virus replicase mutants reveals alphavirus replication complexity and supports antiviral tool development.PLoS pathogens · 2025Article
- Alphavirus nsP2: A Multifunctional Regulator of Viral Replication and Promising Target for Anti-Alphavirus Therapies.Reviews in medical virology · 2025Review
- A robust fluorogenic substrate for chikungunya virus protease (nsP2) activity.Protein science : a publication of the Protein Society · 2025Article
- Alphavirus nsP3 organizes into tubular scaffolds essential for infection and the cytoplasmic granule architecture.Nature communications · 2024Article
- Article
- Alphavirus-based replicons demonstrate different interactions with host cells and can be optimized to increase protein expression.Journal of virology · 2023Article
- Dancing with the Devil: A Review of the Importance of Host RNA-Binding Proteins to Alphaviral RNAs during Infection.Viruses · 2023Review
- Molecular Virology of Chikungunya Virus.Current topics in microbiology and immunology · 2022Review
- The C-Terminal Domain of Salmonid Alphavirus Nonstructural Protein 2 (nsP2) Is Essential and Sufficient To Block RIG-I Pathway Induction and Interferon-Mediated Antiviral Response.Journal of virology · 2021Article
- nsP4 Is a Major Determinant of Alphavirus Replicase Activity and Template Selectivity.Journal of virology · 2021Article
- Facile method for delivering chikungunya viral replicons into mosquitoes and mammalian cells.Scientific reports · 2021Article
- Sensitivity of Alphaviruses to G3BP Deletion Correlates with Efficiency of Replicase Polyprotein Processing.Journal of virology · 2020Article
- Mechanisms of Innate Immune Activation by a Hybrid Alphavirus-Rhabdovirus Vaccine Platform.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2020Article
- Lack of nsP2-specific nuclear functions attenuates chikungunya virus replication both in vitro and in vivo.Virology · 2019Article
- ZAP's stress granule localization is correlated with its antiviral activity and induced by virus replication.PLoS pathogens · 2019Article
- Novel Mutations in nsP2 Abolish Chikungunya Virus-Induced Transcriptional Shutoff and Make the Virus Less Cytopathic without Affecting Its Replication Rates.Journal of virology · 2019Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
One of the distinguishing features of the alphaviruses is a sequential processing of the nonstructural polyproteins P1234 and P123. In the early stages of the infection, the complex of P123+nsP4 forms the primary replication complexes (RCs) that function in negative-strand RNA synthesis. The following processing steps make nsP1+P23+nsP4, and later nsP1+nsP2+nsP3+nsP4. The latter mature complex is active in positive-strand RNA synthesis but can no longer produce negative strands. However, the regulation of negative- and positive-strand RNA synthesis apparently is not the only function of ns polyprotein processing. In this study, we developed Sindbis virus mutants that were incapable of either P23 or P123 cleavage. Both mutants replicated in BHK-21 cells to levels comparable to those of the cleavage-competent virus. They continuously produced negative-strand RNA, but its synthesis was blocked by the translation inhibitor cycloheximide. Thus, after negative-strand synthesis, the ns proteins appeared to irreversibly change conformation and formed mature RCs, in spite of the lack of ns polyprotein cleavage. However, in the cells having no defects in alpha/beta interferon (IFN-alpha/beta) production and signaling, the cleavage-deficient viruses induced a high level of type I IFN and were incapable of causing the spread of infection. Moreover, the P123-cleavage-deficient virus was readily eliminated, even from the already infected cells. We speculate that this inability of the viruses with unprocessed polyprotein to productively replicate in the IFN-competent cells and in the cells of mosquito origin was an additional, important factor in ns polyprotein cleavage development. In the case of the Old World alphaviruses, it leads to the release of nsP2 protein, which plays a critical role in inhibiting the cellular antiviral response.
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.