ArticlePLoS biology2018
Destabilized adaptive influenza variants critical for innate immune system escape are potentiated by host chaperones.
Article in PLoS biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Dominant-negative TP53 mutations potentiated by the HSF1-regulated proteostasis network.Molecular cell · 2026Article
- The immune-evasive proline-283 substitution in influenza nucleoprotein increases aggregation propensity without altering the native structure.Science advances · 2024Article
- Epistasis and pleiotropy shape biophysical protein subspaces associated with drug resistance.Physical review. E · 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
- Epistasis meets pleiotropy in shaping biophysical protein subspaces associated with antimicrobial resistance.bioRxiv : the preprint server for biology · 2023Article
- Article
- Exploring the expanse between theoretical questions and experimental approaches in the modern study of evolvability.Journal of experimental zoology. Part B, Molecular and developmental evolution · 2023Article
- DeGlyPHER: Highly sensitive site-specific analysis of N-linked glycans on proteins.Methods in enzymology · 2023Article
- Article
- GroEL/S Overexpression Helps to Purge Deleterious Mutations and Reduce Genetic Diversity during Adaptive Protein Evolution.Molecular biology and evolution · 2022Article
- Altered transcriptional responses in the lungs of aged mice after influenza infection.Immunity & ageing : I & A · 2022Article
- Thermal Proteome Profiling Reveals the O-GlcNAc-Dependent Meltome.Journal of the American Chemical Society · 2022Article
- The endoplasmic reticulum proteostasis network profoundly shapes the protein sequence space accessible to HIV envelope.PLoS biology · 2022Article
- Possible Therapeutic Intervention Strategies for COVID-19 by Manipulating the Cellular Proteostasis Network.Advances in experimental medicine and biology · 2021Article
- Recent advances in understanding the role of proteostasis.Faculty reviews · 2021Review
- Tick-transmitted thogotovirus gains high virulence by a single MxA escape mutation in the viral nucleoprotein.PLoS pathogens · 2020Article
- HSF1 Activation Can Restrict HIV Replication.ACS infectious diseases · 2020Article
- Chemical Biology Framework to Illuminate Proteostasis.Annual review of biochemistry · 2020Review
- Proteostasis in Viral Infection: Unfolding the Complex Virus-Chaperone Interplay.Cold Spring Harbor perspectives in biology · 2020Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
The threat of viral pandemics demands a comprehensive understanding of evolution at the host-pathogen interface. Here, we show that the accessibility of adaptive mutations in influenza nucleoprotein at fever-like temperatures is mediated by host chaperones. Particularly noteworthy, we observe that the Pro283 nucleoprotein variant, which (1) is conserved across human influenza strains, (2) confers resistance to the Myxovirus resistance protein A (MxA) restriction factor, and (3) critically contributed to adaptation to humans in the 1918 pandemic influenza strain, is rendered unfit by heat shock factor 1 inhibition-mediated host chaperone depletion at febrile temperatures. This fitness loss is due to biophysical defects that chaperones are unavailable to address when heat shock factor 1 is inhibited. Thus, influenza subverts host chaperones to uncouple the biophysically deleterious consequences of viral protein variants from the benefits of immune escape. In summary, host proteostasis plays a central role in shaping influenza adaptation, with implications for the evolution of other viruses, for viral host switching, and for antiviral drug development.
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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.