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Pathogenesis and Immunity

Lethality to Ferrets of H5N1 Influenza Viruses Isolated from Humans and Poultry in 2004

Elena A. Govorkova, Jerold E. Rehg, Scott Krauss, Hui-Ling Yen, Yi Guan, Malik Peiris, Tien D. Nguyen, Thi H. Hanh, Pilipan Puthavathana, Hoang T. Long, Chantanee Buranathai, Wilina Lim, Robert G. Webster, Erich Hoffmann
Elena A. Govorkova
1Departments of Infectious Diseases
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Jerold E. Rehg
2Pathology, St. Jude Children's Research Hospital
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Scott Krauss
1Departments of Infectious Diseases
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Hui-Ling Yen
1Departments of Infectious Diseases
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Yi Guan
3Joint Influenza Research Center (Shantou University Medical College and Hong Kong University), Shantou University Medical College, Shantou, Guangdong
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Malik Peiris
3Joint Influenza Research Center (Shantou University Medical College and Hong Kong University), Shantou University Medical College, Shantou, Guangdong
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Tien D. Nguyen
4Department of Virology, National Institute of Veterinary Research, Ministry of Agriculture and Rural Development
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Thi H. Hanh
5Virology Department, National Institute of Hygiene and Epidemiology, Hanoi, Vietnam
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Pilipan Puthavathana
6Department of Microbiology, Sriraj Hospital
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Hoang T. Long
5Virology Department, National Institute of Hygiene and Epidemiology, Hanoi, Vietnam
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Chantanee Buranathai
7Department of Livestock Development, National Institute of Animal Health, Bangkok, Thailand
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Wilina Lim
8Government Virus Unit, Department of Health, Hong Kong, Special Administrative Region, People's Republic of China
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Robert G. Webster
1Departments of Infectious Diseases
9Department of Pathology, University of Tennessee, Memphis, Tennessee
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  • For correspondence: robert.webster@stjude.org
Erich Hoffmann
1Departments of Infectious Diseases
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DOI: 10.1128/JVI.79.4.2191-2198.2005
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This article has a correction. Please see:

  • Lethality to Ferrets of H5N1 Influenza Viruses Isolated from Humans and Poultry in 2004 - May 26, 2006

ABSTRACT

The 2004 outbreaks of H5N1 influenza viruses in Vietnam and Thailand were highly lethal to humans and to poultry; therefore, newly emerging avian influenza A viruses pose a continued threat, not only to avian species but also to humans. We studied the pathogenicity of four human and nine avian H5N1/04 influenza viruses in ferrets (an excellent model for influenza studies). All four human isolates were fatal to intranasally inoculated ferrets. The human isolate A/Vietnam/1203/04 (H5N1) was the most pathogenic isolate; the severity of disease was associated with a broad tissue tropism and high virus titers in multiple organs, including the brain. High fever, weight loss, anorexia, extreme lethargy, and diarrhea were observed. Two avian H5N1/04 isolates were as pathogenic as the human viruses, causing lethal systemic infections in ferrets. Seven of nine H5N1/04 viruses isolated from avian species caused mild infections, with virus replication restricted to the upper respiratory tract. All chicken isolates were nonlethal to ferrets. A sequence analysis revealed polybasic amino acids in the hemagglutinin connecting peptides of all H5N1/04 viruses, indicating that multiple molecular differences in other genes are important for a high level of virulence. Interestingly, the human A/Vietnam/1203/04 isolate had a lysine substitution at position 627 of PB2 and had one to eight amino acid changes in all gene products except that of the M1 gene, unlike the A/chicken/Vietnam/C58/04 and A/quail/Vietnam/36/04 viruses. Our results indicate that viruses that are lethal to mammals are circulating among birds in Asia and suggest that pathogenicity in ferrets, and perhaps humans, reflects a complex combination of different residues rather than a single amino acid difference.

  • Copyright © 2005 American Society for Microbiology
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Lethality to Ferrets of H5N1 Influenza Viruses Isolated from Humans and Poultry in 2004
Elena A. Govorkova, Jerold E. Rehg, Scott Krauss, Hui-Ling Yen, Yi Guan, Malik Peiris, Tien D. Nguyen, Thi H. Hanh, Pilipan Puthavathana, Hoang T. Long, Chantanee Buranathai, Wilina Lim, Robert G. Webster, Erich Hoffmann
Journal of Virology Jan 2005, 79 (4) 2191-2198; DOI: 10.1128/JVI.79.4.2191-2198.2005

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Lethality to Ferrets of H5N1 Influenza Viruses Isolated from Humans and Poultry in 2004
Elena A. Govorkova, Jerold E. Rehg, Scott Krauss, Hui-Ling Yen, Yi Guan, Malik Peiris, Tien D. Nguyen, Thi H. Hanh, Pilipan Puthavathana, Hoang T. Long, Chantanee Buranathai, Wilina Lim, Robert G. Webster, Erich Hoffmann
Journal of Virology Jan 2005, 79 (4) 2191-2198; DOI: 10.1128/JVI.79.4.2191-2198.2005
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KEYWORDS

Hemagglutinin Glycoproteins, Influenza Virus
Influenza A Virus, H5N1 Subtype
influenza A virus
Influenza, Human
orthomyxoviridae
Poultry Diseases

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