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Pathogenesis and Immunity

A Mouse Model for the Evaluation of Pathogenesis and Immunity to Influenza A (H5N1) Viruses Isolated from Humans

Xiuhua Lu, Terrence M. Tumpey, Timothy Morken, Sherif R. Zaki, Nancy J. Cox, Jacqueline M. Katz
Xiuhua Lu
Influenza Branch and
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Terrence M. Tumpey
Influenza Branch and
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Timothy Morken
Infectious Disease Pathology Activity,Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333
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Sherif R. Zaki
Infectious Disease Pathology Activity,Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333
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Nancy J. Cox
Influenza Branch and
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Jacqueline M. Katz
Influenza Branch and
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DOI: 10.1128/JVI.73.7.5903-5911.1999
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ABSTRACT

During 1997 in Hong Kong, 18 human cases of respiratory illness, including 6 fatalities, were caused by highly pathogenic avian influenza A (H5N1) viruses. Since H5 viruses had previously been isolated only from avian species, the outbreak raised questions about the ability of these viruses to cause severe disease and death in humans. To better understand the pathogenesis and immunity to these viruses, we have used the BALB/c mouse model. Four H5N1 viruses replicated equally well in the lungs of mice without prior adaptation but differed in lethality for mice. H5N1 viruses that were highly lethal for mice were detected in multiple organs, including the brain. This is the first demonstration of an influenza A virus that replicates systemically in a mammalian species and is neurotropic without prior adaptation. The mouse model was also used to evaluate a strategy of vaccination against the highly pathogenic avian H5N1 viruses, using an inactivated vaccine prepared from nonpathogenic A/Duck/Singapore-Q/F119-3/97 (H5N3) virus that was antigenically related to the human H5N1 viruses. Mice administered vaccine intramuscularly, with or without alum, were completely protected from lethal challenge with H5N1 virus. Protection from infection was also observed in 70% of animals administered vaccine alone and 100% of mice administered vaccine with alum. The protective effect of vaccination correlated with the level of virus-specific serum antibody. These results suggests a strategy of vaccine preparedness for rapid intervention in future influenza pandemics that uses antigenically related nonpathogenic viruses as vaccine candidates.

  • Copyright © 1999 American Society for Microbiology
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A Mouse Model for the Evaluation of Pathogenesis and Immunity to Influenza A (H5N1) Viruses Isolated from Humans
Xiuhua Lu, Terrence M. Tumpey, Timothy Morken, Sherif R. Zaki, Nancy J. Cox, Jacqueline M. Katz
Journal of Virology Jul 1999, 73 (7) 5903-5911; DOI: 10.1128/JVI.73.7.5903-5911.1999

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A Mouse Model for the Evaluation of Pathogenesis and Immunity to Influenza A (H5N1) Viruses Isolated from Humans
Xiuhua Lu, Terrence M. Tumpey, Timothy Morken, Sherif R. Zaki, Nancy J. Cox, Jacqueline M. Katz
Journal of Virology Jul 1999, 73 (7) 5903-5911; DOI: 10.1128/JVI.73.7.5903-5911.1999
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KEYWORDS

Influenza A Virus, H5N1 Subtype
influenza A virus
Influenza, Human

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