effect of 1918 pb1-f2 expression on influenza a virus infection kinetics影响1918年pb1-f2表情甲型流感病毒感染动力学.pdfVIP

Effect of 1918 PB1-F2 Expression on Influenza A Virus Infection Kinetics 1 2 3 4 1 Amber M. Smith , Frederick R. Adler , Julie L. McAuley , Ryan N. Gutenkunst , Ruy M. Ribeiro , 5 1 Jonathan A. McCullers , Alan S. Perelson * 1Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America, 2 Departments of Mathematics and Biology, University of Utah, Salt Lake City, Utah, United States of America, 3 Department of Immunology and Microbiology, University of Melbourne, Victoria, Australia, 4 Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona, United States of America, 5 Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, Tennessee, United States of America 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,