Effect of 1918 PB1-F2 expression on influenza A virus infection kinetics.
| Autor: | Amber M Smith, Frederick R Adler, Julie L McAuley, Ryan N Gutenkunst, Ruy M Ribeiro, Jonathan A McCullers, Alan S Perelson |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | PLoS Computational Biology, Vol 7, Iss 2, p e1001081 (2011) |
| Druh dokumentu: | article |
| ISSN: | 1553-734X 1553-7358 |
| DOI: | 10.1371/journal.pcbi.1001081 |
| Popis: | 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. |
| Databáze: | Directory of Open Access Journals |
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