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

Author:

Govorkova Elena A.1,Rehg Jerold E.2,Krauss Scott1,Yen Hui-Ling1,Guan Yi3,Peiris Malik3,Nguyen Tien D.4,Hanh Thi H.5,Puthavathana Pilipan6,Long Hoang T.5,Buranathai Chantanee7,Lim Wilina8,Webster Robert G.19,Hoffmann Erich1

Affiliation:

1. Departments of Infectious Diseases

2. Pathology, St. Jude Children's Research Hospital

3. Joint Influenza Research Center (Shantou University Medical College and Hong Kong University), Shantou University Medical College, Shantou, Guangdong

4. Department of Virology, National Institute of Veterinary Research, Ministry of Agriculture and Rural Development

5. Virology Department, National Institute of Hygiene and Epidemiology, Hanoi, Vietnam

6. Department of Microbiology, Sriraj Hospital

7. Department of Livestock Development, National Institute of Animal Health, Bangkok, Thailand

8. Government Virus Unit, Department of Health, Hong Kong, Special Administrative Region, People's Republic of China

9. Department of Pathology, University of Tennessee, Memphis, Tennessee

Abstract

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.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

Cited by 288 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3