CoChat
Sign Up
Cited by 391Influenza Virus Research StudiesRespiratory viral infections researchVirology and Viral Diseases

Expression of the 1918 influenza A virus PB1-F2 enhances the pathogenesis of viral and secondary bacterial pneumonia

Open access
McAuley, Julie L., Hornung, Felicita, Boyd, Kelli L., Smith, Amber M., McKeon, Raelene, Bennink, Jack, Yewdell, Jonathan W., McCullers, Jonathan A.·2007·Cell Host & Microbe
DOI 10.1016/j.chom.2007.09.001PMC PMC2083255
Open this paper in CoChat — free accountOpen PDF

Abstract

Secondary bacterial pneumonia frequently claimed the lives of victims during the devastating 1918 influenza A virus pandemic. Little is known about the viral factors contributing to the lethality of the 1918 pandemic. Here we show that expression of the viral accessory protein PB1-F2 enhances inflammation during primary viral infection of mice and increases both the frequency and severity of secondary bacterial pneumonia. The priming effect of PB1-F2 on bacterial pneumonia could be recapitulated in mice by intranasal delivery of a synthetic peptide derived from the C-terminal portion of the PB1-F2. Relative to its isogenic parent, an influenza virus engineered to express a PB1-F2 with coding changes matching the 1918 pandemic strain was more virulent in mice, induced more pulmonary immunopathology, and led to more severe secondary bacterial pneumonia. These findings help explain both the unparalleled virulence of the 1918 strain and the high incidence of fatal pneumonia during the pandemic.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.chom.2007.09.001

Cites

39 of 39 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In the staphylococcal superinfection model, lack of PB1-F2 significantly decreased mortality either using an isogenic virus or using the novel pandemic H1N1 strain that does not code for full-length PB1-F2, whereas expression of the more inflammatory PB1-F2 from the 1918 pandemic strain increased mortality.

    “Similarly, in the staphylococcal superinfection model, lack of PB1-F2 significantly decreased mortality either using an isogenic virus (Figure 5A) or using the novel pandemic H1N1 strain that does not code for full-length PB1-F2 (Figure 5B) [34], whereas expression of the more inflammatory PB1-F2 [25] from the 1918 pandemic strain increased mortality.”

    From Influenza virus primes mice for pneumonia from Staphylococcus aureus. (2011) · cites this paper as [25]

  • The viral cytotoxin PB1-F2 contributed to mortality in this model in a manner similar to that seen with pneumococcus, and expression of the pandemic 1918 PB1-F2 enhanced mortality.

    “The viral cytotoxin PB1-F2 contributed to mortality in this model in a manner similar to that seen with pneumococcus [25], and expression of the pandemic 1918 PB1-F2 enhanced mortality.”

    From Influenza virus primes mice for pneumonia from Staphylococcus aureus. (2011) · cites this paper as [25]

  • In both the pneumococcal and staphylococcal models, enhanced inflammatory responses seem to be important in potentiating disease when the virus and the superinfecting bacteria are present together.

    “In both models, enhanced inflammatory responses seem to be important in potentiating disease when the virus and the superinfecting bacteria are present together [25].”

    From Influenza virus primes mice for pneumonia from Staphylococcus aureus. (2011) · cites this paper as [25]

  • In the pneumococcal secondary infection model, increased inflammatory responses caused by expression of the influenza virus cytotoxin PB1-F2 contributed to morbidity and mortality.

    “We had previously revealed, with use of the pneumococcal secondary infection model, that the increased inflammatory responses caused by expression of the influenza virus cytotoxin PB1-F2 contributed to morbidity and mortality [25].”

    From Influenza virus primes mice for pneumonia from Staphylococcus aureus. (2011) · cites this paper as [25]

  • Roughly 3-10 days after viral infection, a proinflammatory state characterized by granulocyte and monocyte influx into the lungs amplifies host responses to bacteria, resulting in poor outcomes.

    “Roughly 3-10 days after viral infection, a proinflammatory state characterized by granulocyte and monocyte influx into the lungs amplifies host responses to bacteria, resulting in poor outcomes [23,25,43].”

    From Influenza virus primes mice for pneumonia from Staphylococcus aureus. (2011) · cites this paper as [25]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
McAuley, J. L., Hornung, F., Boyd, K. L., Smith, A. M., McKeon, R., Bennink, J., Yewdell, J. W., & McCullers, J. A.
Affiliations
  • St. Jude Children's Research Hospital (US)
  • National Institute of Allergy and Infectious Diseases (US)
  • University of Utah (US)
Corresponding author
McCullers, Jonathan A.
ORCID
Venue
Cell Host & Microbe
Publisher
Elsevier BV
Published
2007-10
Volume
2
Issue
4
Pages
240-249
ISSN
1931-3128 (ISSN-L)
DOI
10.1016/j.chom.2007.09.001
PMC
PMC2083255
OpenAlex
W1988457839
Cited by
389
References
39
Citations by year
2026: 4 · 2025: 3 · 2024: 18 · 2023: 8 · 2022: 11 · 2021: 17 · 2020: 10 · 2019: 13 · 2018: 22 · 2017: 18 · 2016: 22 · 2015: 22 · 2014: 23 · 2013: 33 · 2012: 31
FWCI
21.78
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Host & Microbe (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • American Lebanese Syrian Associated Charities
  • National Institutes of Health
  • National Institute of Allergy and Infectious Diseases (AI-54802, AI66349, R21AI054802, R01AI066349)
Topics
  • Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
  • Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
  • Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
Keywords
PB1-F2, viral accessory proteins, secondary bacterial pneumonia, viral pathogenesis, lung inflammation, immunopathology, virulence, synthetic peptides, bacterial co-infection
MeSH terms
Animals, Female, Inflammation, Mice, Inbred BALB C, Orthomyxoviridae Infections, Peptides, Pneumonia, Pneumococcal, Recombinant Proteins, Streptococcus pneumoniae, Viral Proteins, Virulence, Mice, Influenza A Virus, H1N1 Subtype

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review