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Abstract

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.

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This work was partially supported by grants from the NIH to P.P., A.G.-S., C.F.B., and J.K.T. In the Ellison Medical Foundation Program in Global Infectious Diseases, P.P. is a Senior Fellow and C.F.B. is a New Scholar. This work was partially supported by USDA/ARS Current Research Information System (CRIS) project number 6612-32000-039-00D and by National Institute of Allergy and Infectious Diseases (NIAID) cooperative agreements with the Northeastern Biodefense Center (U54 AI57158) and with the Center for Investigating Viral Immunity and Antagonism (CIVIA) (U19 AI62623), as well as by NIAID grant P01 AI058113-01.

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Published In

Science
Volume 310 | Issue 5745
7 October 2005

Submission history

Received: 26 August 2005
Accepted: 20 September 2005
Published in print: 7 October 2005

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Notes

Supporting Online Material
www.sciencemag.org/cgi/content/full/310/5745/77/DC1
Materials and Methods
Fig. S1
Table S1
References and Notes

Authors

Affiliations

Terrence M. Tumpey* [email protected]
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.
Christopher F. Basler
Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Patricia V. Aguilar
Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Hui Zeng
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.
Alicia Solórzano
Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA.
David E. Swayne
Southeast Poultry Research Laboratory, Agricultural Research Laboratory (ARS), U.S. Department of Agriculture (USDA), 934 College Station Road, Athens, GA 30606, USA.
Nancy J. Cox
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.
Jacqueline M. Katz
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.
Jeffery K. Taubenberger
Department of Molecular Pathology, Armed Forces Institute of Pathology, Rockville, MD 20850, USA.
Peter Palese
Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Adolfo García-Sastre
Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA.

Notes

*
To whom correspondence should be addressed. E-mail: [email protected]

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