ArticleJournal of virology2013
Presentation overrides specificity: probing the plasticity of alphaviral proteolytic activity through mutational analysis.
Article in Journal of virology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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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Who cites it
23 citing papers in PubMed, 30 citations in OpenAlex.
- Viral protease-mediated polyprotein processing in human astroviruses.Npj viruses · 2026Article
- The kinetics of nsp7-11 polyprotein processing and impact on complexation with nsp16 among human coronaviruses.Nature communications · 2025Article
- A robust fluorogenic substrate for chikungunya virus protease (nsP2) activity.Protein science : a publication of the Protein Society · 2025Article
- Alphavirus nsP2: A Multifunctional Regulator of Viral Replication and Promising Target for Anti-Alphavirus Therapies.Reviews in medical virology · 2025Review
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- Molecular Virology of Chikungunya Virus.Current topics in microbiology and immunology · 2022Review
- Understanding Molecular Pathogenesis with Chikungunya Virus Research Tools.Current topics in microbiology and immunology · 2022Review
- nsP4 Is a Major Determinant of Alphavirus Replicase Activity and Template Selectivity.Journal of virology · 2021Article
- Semliki Forest Virus Chimeras with Functional Replicase Modules from Related Alphaviruses Survive by Adaptive Mutations in Functionally Important Hot Spots.Journal of virology · 2021Article
- Phosphorylation Sites in the Hypervariable Domain in Chikungunya Virus nsP3 Are Crucial for Viral Replication.Journal of virology · 2021Article
- Sensitivity of Alphaviruses to G3BP Deletion Correlates with Efficiency of Replicase Polyprotein Processing.Journal of virology · 2020Article
- Article
- Timeliness of Proteolytic Events Is Prerequisite for Efficient Functioning of the Alphaviral Replicase.Journal of virology · 2018Article
- A Chikungunya VirusJournal of virology · 2018Article
- Design and Validation of Novel Chikungunya Virus Protease Inhibitors.Antimicrobial agents and chemotherapy · 2016Article
- Chikungunya virus infectivity, RNA replication and non-structural polyprotein processing depend on the nsP2 protease's active site cysteine residue.Scientific reports · 2016Article
- Versatile Trans-Replication Systems for Chikungunya Virus Allow Functional Analysis and Tagging of Every Replicase Protein.PloS one · 2016Article
- Chikungunya nsP2 protease is not a papain-like cysteine protease and the catalytic dyad cysteine is interchangeable with a proximal serine.Scientific reports · 2015Article
- Differences in Processing Determinants of Nonstructural Polyprotein and in the Sequence of Nonstructural Protein 3 Affect Neurovirulence of Semliki Forest Virus.Journal of virology · 2015Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Semliki Forest virus (genus Alphavirus) is an important model for studying regulated nonstructural (ns) polyprotein processing. In this study, we evaluated the strictness of the previously outlined cleavage rules, accounting for the timing and outcome of each of three cleavages within the ns polyprotein P1234, and assessed the significance of residues P6 to P4 within the cleavage sites using an alanine scanning approach. The processing of the 1/2 and 3/4 sites was most strongly affected following changes in residues P5 and P4, respectively. However, none of the mutations had a detectable effect on the processing of the 2/3 site. An analysis of recombinant viruses bearing combinations of mutations in cleavage sites revealed tolerance toward the cooccurrence of native and mutated cleavage sites within the same polyprotein, suggesting a remarkable plasticity of the protease recognition pocket. Even in a virus in which all of the cleavage sequences were replaced with alanines in the P6, P5, and P4 positions, the processing pattern was largely preserved, without leading to reversion of cleavage site mutations. Instead, the emergence of second-site mutations was identified, among which Q706R/L in nsP2 was confirmed to be associated with the recognition of the P4 position within the modified cleavage sites. Our results imply that the spatial arrangement of the viral replication complex inherently contributes to scissile-site presentation for the protease, alleviating stringent sequence recognition requirements yet ensuring the precision and the correct order of processing events. Obtaining a proper understanding of the consequences of cleavage site manipulations may provide new tools for taming alphaviruses.
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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.