ArticleJournal of virology2012
Macromolecular assembly-driven processing of the 2/3 cleavage site in the alphavirus replicase polyprotein.
Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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.
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.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- The life cycle of the alphaviruses: From an antiviral perspective.Antiviral research · 2023Pooled it
- Viral protease-mediated polyprotein processing in human astroviruses.Npj viruses · 2026Article
- 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
- Mimicking superinfection exclusion disrupts alphavirus infection and transmission in the yellow fever mosquitoProceedings of the National Academy of Sciences of the United States of America · 2023Article
- MBZM-N-IBT, a Novel Small Molecule, Restricts Chikungunya Virus Infection by Targeting nsP2 Protease ActivityAntimicrobial agents and chemotherapy · 2022Article
- Article
- Understanding Molecular Pathogenesis with Chikungunya Virus Research Tools.Current topics in microbiology and immunology · 2022Review
- Molecular Virology of Chikungunya Virus.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
- Review
- Interdomain Flexibility of Chikungunya Virus nsP2 Helicase-Protease Differentially Influences Viral RNA Replication and Infectivity.Journal of virology · 2021Article
- Cross-utilisation of template RNAs by alphavirus replicases.PLoS pathogens · 2020Article
- ADP-ribosyl-binding and hydrolase activities of the alphavirus nsP3 macrodomain are critical for initiation of virus replication.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Article
- A Chikungunya VirusJournal of virology · 2018Article
- Timeliness of Proteolytic Events Is Prerequisite for Efficient Functioning of the Alphaviral Replicase.Journal of virology · 2018Article
- Viral Macrodomains: Unique Mediators of Viral Replication and Pathogenesis.Trends in microbiology · 2018Review
- The Enigmatic Alphavirus Non-Structural Protein 3 (nsP3) Revealing Its Secrets at Last.Viruses · 2018Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Semliki Forest virus (SFV) is a member of the Alphavirus genus, which produces its replicase proteins in the form of a nonstructural (ns) polyprotein precursor P1234. The maturation of the replicase occurs in a temporally controlled manner by protease activity of nsP2. The template preference and enzymatic capabilities of the alphaviral replication complex have a very important connection with its composition, which is irreversibly altered by proteolysis. The final cleavage of the 2/3 site in the ns polyprotein apparently leads to significant rearrangements within the replication complex and thus denotes the "point of no return" for viral replication progression. Numerous studies have devised rules for when and how ns protease acts, but how the alphaviral 2/3 site is recognized remained largely unexplained. In contrast to the other two cleavage sites within the ns polyprotein, the 2/3 site evidently lacks primary sequence elements in the vicinity of the scissile bond sufficient for specific protease recognition. In this study, we sought to investigate the molecular details of the regulation of the 2/3 site processing in the SFV ns polyprotein. We present evidence that correct macromolecular assembly, presumably strengthened by exosite interactions rather than the functionality of the individual nsP2 protease, is the driving force for specific substrate targeting. We conclude that structural elements within the macrodomain of nsP3 are used for precise positioning of a substrate recognition sequence at the catalytic center of the protease and that this process is coordinated by the exact N-terminal end of nsP2, thus representing a unique regulation mechanism used by 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.