Evidence map›Paper›PMID 39817904›Full record

ArticleCell reports2025

Probing the functional constraints of influenza A virus NEP by deep mutational scanning.

Qi Wen Teo, Yiquan Wang, Huibin Lv, Michael S Oade, Kevin J Mao, Timothy J C Tan, Yang Wei Huan, Joel Rivera-Cardona, Evan K Shao, Danbi Choi and 5 more

Abstract read
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Review
  5. 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

15 authors.

Qi Wen TeoDepartment of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
Yiquan WangDepartment of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
Huibin LvDepartment of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
Michael S OadeDepartment of Molecular Biology, Princeton University, Washington Road, Princeton, NJ 08544, USA.
Kevin J MaoDepartment of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
Timothy J C TanCenter for Biophysics and Quantitative Biology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
Yang Wei HuanDepartment of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
Joel Rivera-CardonaDepartment of Microbiology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
Evan K ShaoDepartment of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
Danbi ChoiDepartment of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
Chaoyang WangDepartment of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
Zahra Tavakoli DarganiDepartment of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
Christopher B BrookeCarl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Department of Microbiology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
Aartjan J W Te VelthuisDepartment of Molecular Biology, Princeton University, Washington Road, Princeton, NJ 08544, USA.
Nicholas C WuDepartment of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Center for Biophysics and Quantitative Biology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Carle Illinois College of Medicine, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA. Electronic address: nicwu@illinois.edu.

Funding

Structure and dynamics of RNA elements regulating viral aberrant RNA synthesisDP2AI175474 · NIAID · PRINCETON UNIVERSITY · PI TE VELTHUIS, AREND JAN · 2022 to 2025
$2.4M
Biophysical constraints of influenza neuraminidase evolutionR01AI165475 · NIAID · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI WU, NICHOLAS C. · 2022 to 2025
$2.0M
The effects of influenza virus genomic heterogeneity on replication dynamics and the host responseR01AI139246 · NIAID · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI BROOKE, CHRISTOPHER BYRON · 2018 to 2022
$1.9M
NIAID NIH HHS DP2 AI175474NIAID NIH HHS R01 AI139246NIAID NIH HHS R01 AI165475
6 · The paper itself

Abstract

The influenza A virus nuclear export protein (NEP) is a multifunctional protein that is essential for the viral life cycle and has very high sequence conservation. However, since the open reading frame of NEP largely overlaps with that of another influenza viral protein, non-structural protein 1, it is difficult to infer the functional constraints of NEP based on sequence conservation analysis. In addition, the N-terminal of NEP is structurally disordered, which further complicates the understanding of its function. Here, we systematically measure the replication fitness effects of >1,800 mutations of NEP. Our results show that the N-terminal domain has high mutational tolerance. Additional experiments show that N-terminal domain mutations affect viral transcription and replication dynamics, host cellular responses, and mammalian adaptation of avian influenza virus. Overall, our study not only advances the functional understanding of NEP but also provides insights into its evolutionary constraints.

Indexed as

Influenza A virusMutationViral ProteinsAnimalsDogsHumansMadin Darby Canine Kidney CellsVirus ReplicationViral Proteinscellular apoptosisCP: MicrobiologyCP: Molecular biologyevolutionary constraintsinfluenza virusinnate immune responsemammalian adaptation of avian influenza virusNEPNS1nuclear export proteinthe transcription-to-replication switch

Identifiers

PMID39817904
PMCPMC11830162

What OpenQuestion holds

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Registered trials

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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.