ArticlePLoS pathogens2017
Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 75 citations in OpenAlex.
- Comparative analysis of deep mutational scanning datasets in enteroviruses A and B identifies functional divergence and therapeutic targets.Nature ecology & evolution · 2026Article
- Evolution, spread and impact of highly pathogenic H5 avian influenza A viruses.Nature reviews. Microbiology · 2026Review
- The potential of H5N1 viruses to adapt to bovine cells varies throughout evolution.Nature communications · 2025Article
- Differential Host Responses and Viral Replication of Highly Pathogenic Avian Influenza H5N1 Strains in Diverse Cell Lines with a Raw Milk Supplement.Life (Basel, Switzerland) · 2025Article
- Comparative Analysis of Deep Mutational Scanning Datasets in Enteroviruses A and B Identifies Functional Divergence and Therapeutic Targets.Research square · 2025Article
- An ancient influenza genome from Switzerland allows deeper insights into host adaptation during the 1918 flu pandemic in Europe.BMC biology · 2025Article
- The sweet side of H5N1 influenza virus infection.PLoS pathogens · 2025Article
- popDMS infers mutation effects from deep mutational scanning data.Bioinformatics (Oxford, England) · 2024Article
- Bat-borne H9N2 influenza virus evades MxA restriction and exhibits efficient replication and transmission in ferrets.Nature communications · 2024Article
- The immune-evasive proline-283 substitution in influenza nucleoprotein increases aggregation propensity without altering the native structure.Science advances · 2024Article
- PB2 residue 473 contributes to the mammalian virulence of H7N9 avian influenza virus by modulating viral polymerase activity via ANP32A.Journal of virology · 2024Article
- popDMS infers mutation effects from deep mutational scanning data.bioRxiv : the preprint server for biology · 2024Article
- Influenza Virus Host Restriction Factors: The ISGs and Non-ISGs.Pathogens (Basel, Switzerland) · 2024Review
- Tracking a virus' next move.Nature reviews. Microbiology · 2023Article
- Viral Evolution Shaped by Host Proteostasis Networks.Annual review of virology · 2023Review
- Jointly modeling deep mutational scans identifies shifted mutational effects among SARS-CoV-2 spike homologs.bioRxiv : the preprint server for biology · 2023Article
- Anti-influenza A virus restriction factors that shape the human species barrier and virus evolution.PLoS pathogens · 2023Article
- The E2 glycoprotein holds key residues for Mayaro virus adaptation to the urban Aedes aegypti mosquito.PLoS pathogens · 2023Article
- The Antiviral Activity of Equine Mx1 against Thogoto Virus Is Determined by the Molecular Structure of Its Viral Specificity Region.Journal of virology · 2023Article
- The battle for autophagy between host and influenza A virus.Virulence · 2022Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The innate-immune restriction factor MxA inhibits influenza replication by targeting the viral nucleoprotein (NP). Human influenza virus is more resistant than avian influenza virus to inhibition by human MxA, and prior work has compared human and avian viral strains to identify amino-acid differences in NP that affect sensitivity to MxA. However, this strategy is limited to identifying sites in NP where mutations that affect MxA sensitivity have fixed during the small number of documented zoonotic transmissions of influenza to humans. Here we use an unbiased deep mutational scanning approach to quantify how all single amino-acid mutations to NP affect MxA sensitivity in the context of replication-competent virus. We both identify new sites in NP where mutations affect MxA resistance and re-identify mutations known to have increased MxA resistance during historical adaptations of influenza to humans. Most of the sites where mutations have the greatest effect are almost completely conserved across all influenza A viruses, and the amino acids at these sites confer relatively high resistance to MxA. These sites cluster in regions of NP that appear to be important for its recognition by MxA. Overall, our work systematically identifies the sites in influenza nucleoprotein where mutations affect sensitivity to MxA. We also demonstrate a powerful new strategy for identifying regions of viral proteins that affect inhibition by host factors.
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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.