Title |
Effect of 1918 PB1-F2 Expression on Influenza A Virus Infection Kinetics
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Published in |
PLoS Computational Biology, February 2011
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DOI | 10.1371/journal.pcbi.1001081 |
Pubmed ID | |
Authors |
Amber M. Smith, Frederick R. Adler, Julie L. McAuley, Ryan N. Gutenkunst, Ruy M. Ribeiro, Jonathan A. McCullers, Alan S. Perelson |
Abstract |
Relatively little is known about the viral factors contributing to the lethality of the 1918 pandemic, although its unparalleled virulence was likely due in part to the newly discovered PB1-F2 protein. This protein, while unnecessary for replication, increases apoptosis in monocytes, alters viral polymerase activity in vitro, enhances inflammation and increases secondary pneumonia in vivo. However, the effects the PB1-F2 protein have in vivo remain unclear. To address the mechanisms involved, we intranasally infected groups of mice with either influenza A virus PR8 or a genetically engineered virus that expresses the 1918 PB1-F2 protein on a PR8 background, PR8-PB1-F2(1918). Mice inoculated with PR8 had viral concentrations peaking at 72 hours, while those infected with PR8-PB1-F2(1918) reached peak concentrations earlier, 48 hours. Mice given PR8-PB1-F2(1918) also showed a faster decline in viral loads. We fit a mathematical model to these data to estimate parameter values. The model supports a higher viral production rate per cell and a higher infected cell death rate with the PR8-PB1-F2(1918) virus. We discuss the implications these mechanisms have during an infection with a virus expressing a virulent PB1-F2 on the possibility of a pandemic and on the importance of antiviral treatments. |
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Geographical breakdown
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Germany | 3 | 4% |
United Kingdom | 1 | 1% |
Australia | 1 | 1% |
Unknown | 75 | 90% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 29 | 35% |
Student > Ph. D. Student | 16 | 19% |
Student > Master | 8 | 10% |
Student > Bachelor | 5 | 6% |
Professor | 5 | 6% |
Other | 14 | 17% |
Unknown | 6 | 7% |
Readers by discipline | Count | As % |
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Agricultural and Biological Sciences | 23 | 28% |
Medicine and Dentistry | 12 | 14% |
Mathematics | 10 | 12% |
Biochemistry, Genetics and Molecular Biology | 7 | 8% |
Immunology and Microbiology | 4 | 5% |
Other | 15 | 18% |
Unknown | 12 | 14% |