ArticleJournal of virology2015
Molecular Determinants of Virulence and Stability of a Reporter-Expressing H5N1 Influenza A Virus.
Article in Journal of virology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- NS-segment-based reporter influenza A viruses: engineering strategy, applications, and limitations.Journal of virology · 2026Review
- Modification of H1N1 Influenza Luciferase Reporter Viruses Using StopGo Translation and/or Mouse-Adapted Mutations.Viruses · 2025Article
- PB2 and PA mutations contribute to the pathogenicity of mouse-adapted pdmH1N1-Venus reporter influenza A virus in a mammalian model.Frontiers in microbiology · 2024Article
- Real-Time Visualization of the Infection and Replication of a Mouse-Lethal Recombinant H9N2 Avian Influenza Virus.Frontiers in veterinary science · 2022Article
- Full-length genome sequences of the first H9N2 avian influenza viruses isolated in the Northeast of Algeria.Virology journal · 2020Article
- Multicolor two-photon imaging of in vivo cellular pathophysiology upon influenza virus infection using the two-photon IMPRESS.Nature protocols · 2020Article
- Deciphering Molecular Virulence Mechanism of Mycobacterium tuberculosis Dop isopeptidase Based on Its Sequence-Structure-Function Linkage.The protein journal · 2020Article
- High Levels of miR-483-3p Are Present in Serum Exosomes Upon Infection of Mice With Highly Pathogenic Avian Influenza Virus.Frontiers in microbiology · 2020Article
- Inventory of molecular markers affecting biological characteristics of avian influenza A viruses.Virus genes · 2019Review
- Article
- Directed Evolution of an Influenza Reporter Virus To Restore Replication and Virulence and Enhance Noninvasive Bioluminescence Imaging in Mice.Journal of virology · 2018Article
- In vivo imaging of the pathophysiological changes and neutrophil dynamics in influenza virus-infected mouse lungs.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Amino Acid Substitutions HA A150V, PA A343T, and PB2 E627K Increase the Virulence of H5N6 Influenza Virus in Mice.Frontiers in microbiology · 2018Article
- Applications of Replicating-Competent Reporter-Expressing Viruses in Diagnostic and Molecular Virology.Viruses · 2016Review
- Amino acid changes in PB2 and HA affect the growth of a recombinant influenza virus expressing a fluorescent reporter protein.Scientific reports · 2016Article
- Replication-Competent Influenza A and B Viruses Expressing a Fluorescent Dynamic Timer Protein for In Vitro and In Vivo Studies.PloS one · 2016Article
- C646, a Novel p300/CREB-Binding Protein-Specific Inhibitor of Histone Acetyltransferase, Attenuates Influenza A Virus Infection.Antimicrobial agents and chemotherapy · 2015Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
unlabelledWe previously reported that an H5N1 virus carrying the Venus reporter gene, which was inserted into the NS gene segment from the A/Puerto Rico/8/1934(H1N1) virus (Venus-H5N1 virus), became more lethal to mice, and the reporter gene was stably maintained after mouse adaptation compared with the wild-type Venus-H5N1 (WT-Venus-H5N1) virus. However, the basis for this difference in virulence and Venus stability was unclear. Here, we investigated the molecular determinants behind this virulence and reporter stability by comparing WT-Venus-H5N1 virus with a mouse-adapted Venus-H5N1 (MA-Venus-H5N1) virus. To determine the genetic basis for these differences, we used reverse genetics to generate a series of reassortants of these two viruses. We found that reassortants with PB2 from MA-Venus-H5N1 (MA-PB2), MA-PA, or MA-NS expressed Venus more stably than did WT-Venus-H5N1 virus. We also found that a single mutation in PB2 (V25A) or in PA (R443K) increased the virulence of the WT-Venus-H5N1 virus in mice and that the presence of both of these mutations substantially enhanced the pathogenicity of the virus. Our results suggest roles for PB2 and PA in the stable maintenance of a foreign protein as an NS1 fusion protein in influenza A virus. IMPORTANCE: The ability to visualize influenza viruses has far-reaching benefits in influenza virus research. Previously, we reported that an H5N1 virus bearing the Venus reporter gene became more pathogenic to mice and that its reporter gene was more highly expressed and more stably maintained after mouse adaptation. Here, we investigated the molecular determinants behind this enhanced virulence and reporter stability. We found that mutations in PB2 (V25A) and PA (R443K) play crucial roles in the stable maintenance of a foreign protein as an NS1 fusion protein in influenza A virus and in the virulence of influenza virus in mice. Our findings further our knowledge of the pathogenicity of influenza virus in mammals and will help advance influenza virus-related live-imaging studies in vitro and in vivo.
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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.