Evidence map›Paper›PMID 37068231›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2023

Epistasis reduces fitness costs of influenza A virus escape from stem-binding antibodies.

Chung-Young Lee, Vedhika Raghunathan, C Joaquin Caceres, Ginger Geiger, Brittany Seibert, Flavio Cargnin Faccin, L Claire Gay, Lucas M Ferreri, Drishti Kaul, Jens Wrammert and 3 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Chung-Young LeeDepartment of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322.
Vedhika RaghunathanDepartment of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322.ORCID 0000-0002-1484-0524
C Joaquin CaceresDepartment of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.ORCID 0000-0001-8508-6592
Ginger GeigerDepartment of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.
Brittany SeibertDepartment of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.
Flavio Cargnin FaccinDepartment of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.ORCID 0000-0002-5006-5182
L Claire GayDepartment of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.
Lucas M FerreriDepartment of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322.ORCID 0000-0002-1069-9500
Drishti KaulJ. Craig Venter Institute, La Jolla, CA 92037.ORCID 0000-0002-0451-8486
Jens WrammertDivision of Infectious Diseases, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322.
Gene S TanJ. Craig Venter Institute, La Jolla, CA 92037.ORCID 0000-0002-8965-1509
Daniel R PerezDepartment of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.ORCID 0000-0002-6569-5689
Anice C LowenDepartment of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322.ORCID 0000-0002-9829-112X

Funding

Impact of intra-host population structure on influenza virus antigenic evolutionR01AI165644 · NIAID · EMORY UNIVERSITY · PI Anice C Lowen · 2022 to 2026
$1.9M
NIAID NIH HHS HHSN272201400004CNIAID NIH HHS R01 AI165644NIH HHS HHSN272201400004C
6 · The paper itself

Abstract

The hemagglutinin (HA) stem region is a major target of universal influenza vaccine efforts owing to the presence of highly conserved epitopes across multiple influenza A virus (IAV) strains and subtypes. To explore the potential impact of vaccine-induced immunity targeting the HA stem, we examined the fitness effects of viral escape from stem-binding broadly neutralizing antibodies (stem-bnAbs). Recombinant viruses containing each individual antibody escape substitution showed diminished replication compared to wild-type virus, indicating that stem-bnAb escape incurred fitness costs. A second-site mutation in the HA head domain (N129D; H1 numbering) reduced the fitness effects observed in primary cell cultures and likely enabled the selection of escape mutations. Functionally, this putative permissive mutation increased HA avidity for its receptor. These results suggest a mechanism of epistasis in IAV, wherein modulating the efficiency of attachment eases evolutionary constraints imposed by the requirement for membrane fusion. Taken together, the data indicate that viral escape from stem-bnAbs is costly but highlights the potential for epistatic interactions to enable evolution within the functionally constrained HA stem domain.

Indexed as

Influenza A virusInfluenza, HumanInfluenza VaccinesAntibodies, NeutralizingAntibodies, ViralBroadly Neutralizing AntibodiesEpistasis, GeneticHemagglutinin Glycoproteins, Influenza VirusHemagglutininsHumansAntibodies, NeutralizingAntibodies, ViralBroadly Neutralizing AntibodiesHemagglutinin Glycoproteins, Influenza VirusHemagglutininsInfluenza Vaccinesantigenic escapeepistasisevolutionHA steminfluenza A virus

Identifiers

PMID37068231
PMCPMC10151473

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.