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Characterization of the Reconstructed 1918 Spanish Influenza Pandemic Virus
Terrence M. Tumpey,1*Christopher F. Basler,2Patricia V. Aguilar,2Hui Zeng,1Alicia Solórzano,2David E. Swayne,4Nancy J. Cox,1Jacqueline M. Katz,1Jeffery K. Taubenberger,3Peter Palese,2Adolfo García-Sastre2
The pandemic influenza virus of 1918–1919 killed an estimated20 to 50 million people worldwide. With the recent availabilityof the complete 1918 influenza virus coding sequence, we usedreverse genetics to generate an influenza virus bearing alleight gene segments of the pandemic virus to study the propertiesassociated with its extraordinary virulence. In stark contrastto contemporary human influenza H1N1 viruses, the 1918 pandemicvirus had the ability to replicate in the absence of trypsin,caused death in mice and embryonated chicken eggs, and displayeda high-growth phenotype in human bronchial epithelial cells.Moreover, the coordinated expression of the 1918 virus genesmost certainly confers the unique high-virulence phenotype observedwith this pandemic virus.
1 Influenza Branch, Mailstop G-16, Division of Viral and Rickettsial Diseases (DVRD), National Center for Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, NE, Atlanta, GA 30333, USA. 2 Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA. 3 Department of Molecular Pathology, Armed Forces Institute of Pathology, Rockville, MD 20850, USA. 4 Southeast Poultry Research Laboratory, Agricultural Research Laboratory (ARS), U.S. Department of Agriculture (USDA), 934 College Station Road, Athens, GA 30606, USA.
Note added in proof: This research was done by staff takingantiviral prophylaxis and using stringent biosafety precautions(15) to protect the researchers, the environment, and the public.The fundamental purpose of this work was to provide informationcritical to protect public health and to develop measures effectiveagainst future influenza pandemics.
* To whom correspondence should be addressed. E-mail: tft9{at}cdc.gov
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