ArticlePLoS pathogens2010
High-resolution functional mapping of the venezuelan equine encephalitis virus genome by insertional mutagenesis and massively parallel sequencing.
Article in PLoS pathogens, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- Scanning the horizon: deep mutational scanning approaches in virology.Journal of virology · 2026Review
- The Interplay Between Therapeutic Self-Amplifying RNA and the Innate Immune System: Balancing Efficiency and Reactogenicity.International journal of molecular sciences · 2025Review
- Controllable self-replicating RNA vaccine delivered intradermally elicits predominantly cellular immunity.iScience · 2023Article
- Review
- Applications of Deep Mutational Scanning in Virology.Viruses · 2021Review
- Multiple capsid protein binding sites mediate selective packaging of the alphavirus genomic RNA.Nature communications · 2020Article
- Genome-Wide Mutagenesis of Hepatitis C Virus Reveals Ability of Genome To Overcome Detrimental Mutations.Journal of virology · 2020Article
- Recombinant Hepatitis E Viruses Harboring Tags in the ORF1 Protein.Journal of virology · 2019Article
- Conformational plasticity of the VEEV macro domain is important for binding of ADP-ribose.Journal of structural biology · 2019Article
- Random Insertional Mutagenesis of a Serotype 2 Dengue Virus Clone.Bio-protocol · 2018Article
- Functional Analysis of the Dengue Virus Genome Using an Insertional Mutagenesis Screen.Journal of virology · 2018Article
- Transposon Mutagenesis of the Zika Virus Genome Highlights Regions Essential for RNA Replication and Restricted for Immune Evasion.Journal of virology · 2017Article
- Interactions of Alphavirus nsP3 Protein with Host Proteins.Frontiers in microbiology · 2017Review
- Mutational Analysis of Measles Virus Suggests Constraints on Antigenic Variation of the Glycoproteins.Cell reports · 2015Article
- Article
- High-throughput identification of loss-of-function mutations for anti-interferon activity in the influenza A virus NS segment.Journal of virology · 2014Article
- Genome-wide mutagenesis of influenza virus reveals unique plasticity of the hemagglutinin and NS1 proteins.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Imaging of the alphavirus capsid protein during virus replication.Journal of virology · 2013Article
- Systematic identification of H274Y compensatory mutations in influenza A virus neuraminidase by high-throughput screening.Journal of virology · 2013Article
- High-resolution functional profiling of the norovirus genome.Journal of virology · 2012Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have developed a high-resolution genomic mapping technique that combines transposon-mediated insertional mutagenesis with either capillary electrophoresis or massively parallel sequencing to identify functionally important regions of the Venezuelan equine encephalitis virus (VEEV) genome. We initially used a capillary electrophoresis method to gain insight into the role of the VEEV nonstructural protein 3 (nsP3) in viral replication. We identified several regions in nsP3 that are intolerant to small (15 bp) insertions, and thus are presumably functionally important. We also identified nine separate regions in nsP3 that will tolerate small insertions at low temperatures (30°C), but not at higher temperatures (37°C, and 40°C). Because we found this method to be extremely effective at identifying temperature sensitive (ts) mutations, but limited by capillary electrophoresis capacity, we replaced the capillary electrophoresis with massively parallel sequencing and used the improved method to generate a functional map of the entire VEEV genome. We identified several hundred potential ts mutations throughout the genome and we validated several of the mutations in nsP2, nsP3, E3, E2, E1 and capsid using single-cycle growth curve experiments with virus generated through reverse genetics. We further demonstrated that two of the nsP3 ts mutants were attenuated for virulence in mice but could elicit protective immunity against challenge with wild-type VEEV. The recombinant ts mutants will be valuable tools for further studies of VEEV replication and virulence. Moreover, the method that we developed is applicable for generating such tools for any virus with a robust reverse genetics system.
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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.