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Science 7 October 2005:
Vol. 310. no. 5745, pp. 77 - 80
DOI: 10.1126/science.1119392
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Research Articles

Characterization of the Reconstructed 1918 Spanish Influenza Pandemic Virus

Terrence M. Tumpey,1* Christopher F. Basler,2 Patricia V. Aguilar,2 Hui Zeng,1 Alicia Solórzano,2 David E. Swayne,4 Nancy J. Cox,1 Jacqueline M. Katz,1 Jeffery K. Taubenberger,3 Peter Palese,2 Adolfo García-Sastre2

The pandemic influenza virus of 1918–1919 killed an estimated 20 to 50 million people worldwide. With the recent availability of the complete 1918 influenza virus coding sequence, we used reverse genetics to generate an influenza virus bearing all eight gene segments of the pandemic virus to study the properties associated with its extraordinary virulence. In stark contrast to contemporary human influenza H1N1 viruses, the 1918 pandemic virus had the ability to replicate in the absence of trypsin, caused death in mice and embryonated chicken eggs, and displayed a high-growth phenotype in human bronchial epithelial cells. Moreover, the coordinated expression of the 1918 virus genes most certainly confers the unique high-virulence phenotype observed with 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 taking antiviral 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 information critical to protect public health and to develop measures effective against future influenza pandemics.

* To whom correspondence should be addressed. E-mail: tft9{at}cdc.gov

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