The effects of influenza A virus PB1-F2 protein on polymerase activity are strain specific and do not impact pathogenesis
Open accessAbstract
The influenza A virus PB1-F2 protein has been implicated as a virulence factor, but the mechanism by which it enhances pathogenicity is not understood. The PB1 gene segment of the H1N1 swine-origin influenza virus pandemic strain codes for a truncated PB1-F2 protein which terminates after 11 amino acids but could acquire the full-length form by mutation or reassortment. It is therefore important to understand the function and impact of this protein. We systematically assessed the effect that PB1-F2 expression has on viral polymerase activity, accumulation and localization of PB1, and replication in vitro and in mice. We used both the laboratory strain PR8 and a set of viruses engineered to study clinically relevant PB1-F2 proteins. PB1-F2 expression had modest effects on polymerase activity, PB1 accumulation, and replication that were cell type and virus strain dependent. Disruption of the PB1-F2 reading frame in a recent, seasonal H3N2 influenza virus strain did not affect these parameters, suggesting that this is not a universal function of the protein. Disruption of PB1-F2 expression in several backgrounds or expression of PB1-F2 from the 1918 pandemic strain or a 1956 H1N1 strain had no effect on viral lung loads in mice. Alternate mechanisms besides alterations to replication are likely responsible for the enhanced virulence in mammalian hosts attributed to PB1-F2 in previous studies.
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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 [34]
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Influenza virus primes mice for pneumonia from Staphylococcus aureus.
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- Authors
- McAuley, J. L., Zhang, K., & McCullers, J. A.
- Affiliations
- St. Jude Children's Research Hospital (US)
- Corresponding author
- McCullers, Jonathan A.
- ORCID
- McAuley, Julie L.
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2010-01
- Volume
- 84
- Issue
- 1
- Pages
- 558-564
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC2798424
- OpenAlex
- W2074202566
- Cited by
- 110
- References
- 28
- Citations by year
- 2024: 8 · 2022: 4 · 2021: 7 · 2020: 1 · 2019: 2 · 2018: 4 · 2017: 5 · 2016: 8 · 2015: 6 · 2014: 10 · 2013: 8 · 2012: 10
- FWCI
- 10.57
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Virology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Lebanese Syrian Associated Charities
- National Institute of Allergy and Infectious Diseases (AI66349, R01AI066349)
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
- Keywords
- influenza A virus, PB1-F2 protein, viral polymerase activity, viral replication, strain-specific effects, virulence factors, PR8, lung viral load
- MeSH terms
- Animals, DNA-Directed RNA Polymerases, Species Specificity, Viral Proteins, Virulence, Virus Replication, Viral Load, Mice, Influenza A Virus, H1N1 Subtype, Influenza A Virus, H3N2 Subtype
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