Letters to Nature

Nature 430, 209-213 (8 July 2004) | doi:10.1038/nature02746; Received 13 April 2004; Accepted 14 June 2004

Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia

K. S. Li1, Y. Guan1,2, J. Wang1,2, G. J. D. Smith1,2, K. M. Xu1,2, L. Duan1,2, A. P. Rahardjo3, P. Puthavathana4, C. Buranathai5, T. D. Nguyen6, A. T. S. Estoepangestie3, A. Chaisingh5, P. Auewarakul4, H. T. Long7, N. T. H. Hanh7, R. J. Webby8, L. L. M. Poon2, H. Chen1,2, K. F. Shortridge1,2, K. Y. Yuen2, R. G. Webster2,8 & J. S. M. Peiris1,2

  1. Joint Influenza Research Centre (SUMC & HKU), Shantou University Medical College, Shantou, Guangdong 515031, China
  2. Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China
  3. Fakultas Kedokteran Hewan, Universitas Airlangga, Surabaya 60115, Indonesia
  4. Department of Microbiology, Sriraj Hospital, Bangkok 10700, Thailand
  5. Department of Livestock Development, National Institute of Animal Health, Bangkok 10900, Thailand
  6. Department of Virology, National Institute of Veterinary Research, Ministry of Agriculture and Rural Development, Hanoi, Vietnam
  7. Virology Department, National Institute of Hygiene and Epidemiology, Hanoi, Vietnam
  8. Virology Division, Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA

Correspondence to: Y. Guan1,2 Email: yguan@hkucc.hku.hk
The sequences reported in this paper have been deposited in GenBank under accession numbers AY651320–AY651758.

A highly pathogenic avian influenza virus, H5N1, caused disease outbreaks in poultry in China and seven other east Asian countries between late 2003 and early 2004; the same virus was fatal to humans in Thailand and Vietnam1. Here we demonstrate a series of genetic reassortment events traceable to the precursor of the H5N1 viruses that caused the initial human outbreak in Hong Kong in 1997 (refs 2–4) and subsequent avian outbreaks in 2001 and 2002 (refs 5, 6). These events gave rise to a dominant H5N1 genotype (Z) in chickens and ducks that was responsible for the regional outbreak in 2003–04. Our findings indicate that domestic ducks in southern China had a central role in the generation and maintenance of this virus, and that wild birds may have contributed to the increasingly wide spread of the virus in Asia. Our results suggest that H5N1 viruses with pandemic potential have become endemic in the region and are not easily eradicable. These developments pose a threat to public and veterinary health in the region and potentially the world, and suggest that long-term control measures are required.

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