Evidence map›Paper›PMID 25795456›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015

Influenza virus M2 targets cystic fibrosis transmembrane conductance regulator for lysosomal degradation during viral infection.

James David Londino, Ahmed Lazrak, James W Noah, Saurabh Aggarwal, Vedrana Bali, Bradford A Woodworth, Zsuzsanna Bebok, Sadis Matalon

Abstract read
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 1 pooled it
–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

40 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Rhinorrhea and increased chloride secretion through the CFTR chloride channel-a systematic review.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2023
    Pooled it
  2. Proteomic Analysis of Influenza.Advances in experimental medicine and biology · 2026
    Review
  3. Article
  4. Article
  5. Lipopolysaccharide Causes Acquired CFTR Dysfunction in Murine Nasal Airways.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2025
    Article
  6. CFTR as a therapeutic target for severe lung infection.American journal of physiology. Lung cellular and molecular physiology · 2025
    Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
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  15. Article
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  17. Article
  18. Article
  19. Reply to Eisenhut.American journal of physiology. Lung cellular and molecular physiology · 2021
    Article
  20. Article
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

8 authors.

James David Londino*Department of Anesthesiology, Pulmonary Injury and Repair Center, and Department of Cell, Developmental and Integrative Biology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA; Southern Research Institute, Birmingham, Alabama, USA; and Department of Surgery, Division of Otolaryngology, School of Medicine, University of Alabama, Birmingham, Alabama, USA.
Ahmed Lazrak*Department of Anesthesiology, Pulmonary Injury and Repair Center, and Department of Cell, Developmental and Integrative Biology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA; Southern Research Institute, Birmingham, Alabama, USA; and Department of Surgery, Division of Otolaryngology, School of Medicine, University of Alabama, Birmingham, Alabama, USA.
James W Noah*Department of Anesthesiology, Pulmonary Injury and Repair Center, and Department of Cell, Developmental and Integrative Biology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA; Southern Research Institute, Birmingham, Alabama, USA; and Department of Surgery, Division of Otolaryngology, School of Medicine, University of Alabama, Birmingham, Alabama, USA.
Saurabh Aggarwal*Department of Anesthesiology, Pulmonary Injury and Repair Center, and Department of Cell, Developmental and Integrative Biology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA; Southern Research Institute, Birmingham, Alabama, USA; and Department of Surgery, Division of Otolaryngology, School of Medicine, University of Alabama, Birmingham, Alabama, USA.
Vedrana Bali*Department of Anesthesiology, Pulmonary Injury and Repair Center, and Department of Cell, Developmental and Integrative Biology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA; Southern Research Institute, Birmingham, Alabama, USA; and Department of Surgery, Division of Otolaryngology, School of Medicine, University of Alabama, Birmingham, Alabama, USA.
Bradford A Woodworth*Department of Anesthesiology, Pulmonary Injury and Repair Center, and Department of Cell, Developmental and Integrative Biology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA; Southern Research Institute, Birmingham, Alabama, USA; and Department of Surgery, Division of Otolaryngology, School of Medicine, University of Alabama, Birmingham, Alabama, USA.
Zsuzsanna Bebok*Department of Anesthesiology, Pulmonary Injury and Repair Center, and Department of Cell, Developmental and Integrative Biology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA; Southern Research Institute, Birmingham, Alabama, USA; and Department of Surgery, Division of Otolaryngology, School of Medicine, University of Alabama, Birmingham, Alabama, USA.
Sadis Matalon*Department of Anesthesiology, Pulmonary Injury and Repair Center, and Department of Cell, Developmental and Integrative Biology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA; Southern Research Institute, Birmingham, Alabama, USA; and Department of Surgery, Division of Otolaryngology, School of Medicine, University of Alabama, Birmingham, Alabama, USA sadis@uab.edu.

Funding

UAB CF Research and Translation Core CenterP30DK072482 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Brian R. Davis · 2007 to 2026
$23.0M
PATHOPHYSIOLOGY OF SUBLETHAL OXYGEN IN INJURED LUNGSR01HL031197 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI MARK N GILLESPIE, Sadis Matalon · 1985 to 2026
$4.2M
Prevention and Treatment of Chlorine Gas Induced Injury to the Pulmonary SystemU01ES015676 · NIEHS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI MATALON, SADIS · 2006 to 2011
$3.3M
Cell Biology of CFTR in Polarized EpitheliaR01DK060065 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI COLLAWN, JAMES F. · 2003 to 2013
$3.1M
CFTR Biogenesis and Function in EpitheliaR01HL076587 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BEBOK, ZSUZSA · 2004 to 2012
$2.6M
PATHOPHYSIOLOGY OF SUBLETHAL OXYGEN INJURED LUNGSR37HL031197 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI MATALON, SADIS · 1997 to 2006
$2.4M
NHLBI NIH HHS HL031197NHLBI NIH HHS HL076587NHLBI NIH HHS R01 HL031197NHLBI NIH HHS R01 HL076587NHLBI NIH HHS R37 HL031197NIDDK NIH HHS DK60065NIDDK NIH HHS P30 DK072482NIDDK NIH HHS R01 DK060065NIEHS NIH HHS 5U01ES015676NIEHS NIH HHS U01 ES015676
6 · The paper itself

Abstract

We sought to determine the mechanisms by which influenza infection of human epithelial cells decreases cystic fibrosis transmembrane conductance regulator (CFTR) expression and function. We infected human bronchial epithelial (NHBE) cells and murine nasal epithelial (MNE) cells with various strains of influenza A virus. Influenza infection significantly reduced CFTR short circuit currents (Isc) and protein levels at 8 hours postinfection. We then infected CFTR expressing human embryonic kidney (HEK)-293 cells (HEK-293 CFTRwt) with influenza virus encoding a green fluorescent protein (GFP) tag and performed whole-cell and cell-attached patch clamp recordings. Forskolin-stimulated, GlyH-101-sensitive CFTR conductances, and CFTR open probabilities were reduced by 80% in GFP-positive cells; Western blots also showed significant reduction in total and plasma membrane CFTR levels. Knockdown of the influenza matrix protein 2 (M2) with siRNA, or inhibition of its activity by amantadine, prevented the decrease in CFTR expression and function. Lysosome inhibition (bafilomycin-A1), but not proteasome inhibition (lactacystin), prevented the reduction in CFTR levels. Western blots of immunoprecipitated CFTR from influenza-infected cells, treated with BafA1, and probed with antibodies against lysine 63-linked (K-63) or lysine 48-linked (K-48) polyubiquitin chains supported lysosomal targeting. These results highlight CFTR damage, leading to early degradation as an important contributing factor to influenza infection-associated ion transport defects.

Indexed as

AnimalsApoptosisCells, CulturedCystic Fibrosis Transmembrane Conductance RegulatorEpithelial CellsGene ExpressionGene Knockdown TechniquesHEK293 CellsHumansInfluenza A virusInfluenza, HumanIon TransportLysosomesMiceNecrosisPatch-Clamp TechniquesCFTR protein, humanCystic Fibrosis Transmembrane Conductance RegulatorM2 protein, Influenza A virusViral Matrix ProteinsViroporin ProteinsamantadineDsiRNANHBE cellspatch clampshort circuit current

Identifiers

PMID25795456
PMCPMC4478808

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.