ArticleeLife2018
Enhanced ER proteostasis and temperature differentially impact the mutational tolerance of influenza hemagglutinin.
Article in eLife, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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
23 citing papers in PubMed, 36 citations in OpenAlex.
- Dominant-negative TP53 mutations potentiated by the HSF1-regulated proteostasis network.Molecular cell · 2026Article
- Failed Cellular Surveillance Enables Pathogenic Matrix Deposition in abioRxiv : the preprint server for biology · 2025Article
- Protein Quality Control is a Master Modulator of Molecular Evolution in Bacteria.Genome biology and evolution · 2025Review
- The importance of epistasis in the evolution of viral pathogens.Virus evolution · 2025Review
- Protein Glycosylation Patterns Shaped By the IRE1-XBP1s Arm of the Unfolded Protein Response.Israel journal of chemistry · 2024Article
- ER procollagen storage defect without coupled unfolded protein response drives precocious arthritis.Life science alliance · 2024Article
- 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
- Molecular determinants of Hsp90 dependence of Src kinase revealed by deep mutational scanning.Protein science : a publication of the Protein Society · 2023Article
- Genotype-phenotype landscapes for immune-pathogen coevolution.Trends in immunology · 2023Review
- Epistasis meets pleiotropy in shaping biophysical protein subspaces associated with antimicrobial resistance.bioRxiv : the preprint server for biology · 2023Article
- Modulation of Influenza A virus NS1 expression reveals prioritization of host response antagonism at single-cell resolution.Frontiers in microbiology · 2023Article
- DeGlyPHER: Highly sensitive site-specific analysis of N-linked glycans on proteins.Methods in enzymology · 2023Article
- Article
- The endoplasmic reticulum proteostasis network profoundly shapes the protein sequence space accessible to HIV envelope.PLoS biology · 2022Article
- Influenza A viruses balance ER stress with host protein synthesis shutoff.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Deep Mutational Scanning of Viral Glycoproteins and Their Host Receptors.Frontiers in molecular biosciences · 2021Review
- Recent advances in understanding the role of proteostasis.Faculty reviews · 2021Review
- HSF1 Activation Can Restrict HIV Replication.ACS infectious diseases · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
We systematically and quantitatively evaluate whether endoplasmic reticulum (ER) proteostasis factors impact the mutational tolerance of secretory pathway proteins. We focus on influenza hemaggluttinin (HA), a viral membrane protein that folds in the host's ER via a complex pathway. By integrating chemical methods to modulate ER proteostasis with deep mutational scanning to assess mutational tolerance, we discover that upregulation of ER proteostasis factors broadly enhances HA mutational tolerance across diverse structural elements. Remarkably, this proteostasis network-enhanced mutational tolerance occurs at the same sites where mutational tolerance is most reduced by propagation at fever-like temperature. These findings have important implications for influenza evolution, because influenza immune escape is contingent on HA possessing sufficient mutational tolerance to evade antibodies while maintaining the capacity to fold and function. More broadly, this work provides the first experimental evidence that ER proteostasis mechanisms define the mutational tolerance and, therefore, the evolution of secretory pathway proteins.
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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.