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Journal of Virology, May 2002, p. 4420-4429, Vol. 76, No. 9
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.9.4420-4429.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Pathogenesis of Avian Influenza A (H5N1) Viruses in Ferrets

Lois A. Zitzow,1,2,{dagger} Thomas Rowe,1 Timothy Morken,3 Wun-Ju Shieh,3 Sherif Zaki,3 and Jacqueline M. Katz1*

Influenza BranchInfectious Disease Pathology Activity,1 Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333,3 Division of Animal Resources, Emory University, Atlanta, Georgia 303222

Received 29 October 2001/ Accepted 25 January 2002

Highly pathogenic avian influenza A H5N1 viruses caused outbreaks of disease in domestic poultry and humans in Hong Kong in 1997. Direct transmission of the H5N1 viruses from birds to humans resulted in 18 documented cases of respiratory illness, including six deaths. Here we evaluated two of the avian H5N1 viruses isolated from humans for their ability to replicate and cause disease in outbred ferrets. A/Hong Kong/483/97 virus was isolated from a fatal case and was highly pathogenic in the BALB/c mouse model, whereas A/Hong Kong/486/97 virus was isolated from a case with mild illness and exhibited a low-pathogenicity phenotype in mice. Ferrets infected intranasally with 107 50% egg infectious doses (EID50) of either H5N1 virus exhibited severe lethargy, fever, weight loss, transient lymphopenia, and replication in the upper and lower respiratory tract, as well as multiple systemic organs, including the brain. Gastrointestinal symptoms were seen in some animals. In contrast, weight loss and severe lethargy were not noted in ferrets infected with 107 EID50 of two recent human H3N2 viruses, although these viruses were also isolated from the brains, but not other extrapulmonary organs, of infected animals. The results demonstrate that both H5N1 viruses were highly virulent in the outbred ferret model, unlike the differential pathogenicity documented in inbred BALB/c mice. We propose the ferret as an alternative model system for the study of these highly pathogenic avian viruses.

* Corresponding author. Mailing address: Influenza Branch Mailstop G-16, Centers for Disease Control and Prevention, 1600 Clifton Rd., Atlanta, GA 30333. Phone: (404) 639-3591. Fax: (404) 639-2334. E-mail: JKatz{at}cdc.gov.

{dagger} Present address: Center for Comparative Medicine, Baylor College of Medicine, Houston, TX 77030.

Journal of Virology, May 2002, p. 4420-4429, Vol. 76, No. 9
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.9.4420-4429.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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