The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
Expression of the 1918 Influenza A Virus PB1-F2 Enhances the Pathogenesis of Viral and Secondary Bacterial Pneumonia
Open accessAbstract
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.
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“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]
In the citing paper
“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 the citing paper
“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 citing paper
“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]
In the citing paper
“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]
In the citing paper
“There seems to be biphasic response to the virus that alters innate responses to the secondary bacterial pathogen.”
From Influenza virus primes mice for pneumonia from Staphylococcus aureus. (2011) · cites this paper as [25]
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Metadata
- 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.
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2007-10
- Volume
- 2
- Issue
- 4
- Pages
- 240-249
- ISSN
- 1931-3128 (ISSN-L)
- 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
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2116 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- 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
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