ArticleJournal of virology2005
Functional constraints of influenza A virus epitopes limit escape from cytotoxic T lymphocytes.
Article in Journal of virology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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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
54 citing papers in PubMed, 104 citations in OpenAlex.
- Molecular basis for universal HLA-A*0201-restricted CD8+ T-cell immunity against influenza viruses.Proceedings of the National Academy of Sciences of the United States of America · 2016Trial
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- Divergent pathogenic mechanisms of influenza A and influenza B viruses.Archives of microbiology · 2026Review
- Primary Sequence-Intrinsic Immune Evasion by Viral Proteins Guides CTL-Based Vaccine Strategies.Viruses · 2025Review
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- Next-generation T cell-activating vaccination increases influenza virus mutation prevalence.Science advances · 2022Article
- Nucleotide-based genetic networks: Methods and applications.Journal of biosciences · 2022Article
- Role of cross-reactivity in cellular immune targeting of influenza A M1Frontiers in immunology · 2022Article
- Within-host evolutionary dynamics of seasonal and pandemic human influenza A viruses in young children.eLife · 2021Article
- Robust induction of TMolecular therapy. Methods & clinical development · 2021Article
- T Cell Immunity against Influenza: The Long Way from Animal Models Towards a Real-Life Universal Flu Vaccine.Viruses · 2021Review
- Editorial of Harnessing the Power of T Cells: The Promising Hope for a Universal Influenza Vaccine.Vaccines · 2020Article
- Harnessing Cross-Reactive CD8Viral immunology · 2020Article
- Population implications of the deployment of novel universal vaccines against epidemic and pandemic influenza.Journal of the Royal Society, Interface · 2020Article
- Article
- Deep Mutational Scan of the Highly Conserved Influenza A Virus M1 Matrix Protein Reveals Substantial Intrinsic Mutational Tolerance.Journal of virology · 2019Article
- Why Are CD8 T Cell Epitopes of Human Influenza A Virus Conserved?Journal of virology · 2019Article
- Variation at Extra-epitopic Amino Acid Residues Influences Suppression of Influenza Virus Replication by M1Journal of virology · 2018Article
- Harnessing the Power of T Cells: The Promising Hope for a Universal Influenza Vaccine.Vaccines · 2018Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Viruses can exploit a variety of strategies to evade immune surveillance by cytotoxic T lymphocytes (CTL), including the acquisition of mutations in CTL epitopes. Also for influenza A viruses a number of amino acid substitutions in the nucleoprotein (NP) have been associated with escape from CTL. However, other previously identified influenza A virus CTL epitopes are highly conserved, including the immunodominant HLA-A*0201-restricted epitope from the matrix protein, M1(58-66). We hypothesized that functional constraints were responsible for the conserved nature of influenza A virus CTL epitopes, limiting escape from CTL. To assess the impact of amino acid substitutions in conserved epitopes on viral fitness and recognition by specific CTL, we performed a mutational analysis of CTL epitopes. Both alanine replacements and more conservative substitutions were introduced at various positions of different influenza A virus CTL epitopes. Alanine replacements for each of the nine amino acids of the M1(58-66) epitope were tolerated to various extents, except for the anchor residue at the second position. Substitution of anchor residues in other influenza A virus CTL epitopes also affected viral fitness. Viable mutant viruses were used in CTL recognition experiments. The results are discussed in the light of the possibility of influenza viruses to escape from specific CTL. It was speculated that functional constraints limit variation in certain epitopes, especially at anchor residues, explaining the conserved nature of these epitopes.
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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.