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


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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Figure 1
Figure 2: Seasonality of the isolation of avian H5N1 viruses from domestic poultry in mainland China during July 2000 to January 2004 (see Table 1).
Figure 3: The genotypes of H5N1 influenza virus reassortants from eastern Asia.
Figure 4: Phylogenetic relationships of the haemagglutinin (a) and matrix protein (b) genes of representative influenza A viruses isolated in southeastern Asia, including 2 of 6 from Indonesia, 5 of 8 from Thailand and 4 of 12 from Vietnam.


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We acknowledge K. Stöhr and the World Health Organization for facilitating the study; L. J. Zhang, C. L. Cheung and Y. H. C. Leung for technical assistance; N. Ng and colleagues for provision of computing facilities; and T. M. Ellis, K. Dyrting, W. Wong, P. Li and C. Li of the Department of Agriculture, Fisheries and Conservation of Hong Kong for their support of field work and W. Lim, for virus isolates. We also thank S. Naron for editorial assistance. These studies were supported by a grant from the National Institutes of Health, a grant from The Wellcome Trust, the Ellison Foundation, the Li Ka Shing Foundation, and grants from the Research Grants Council of Hong Kong.

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Correspondence to Y. Guan.

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Supplementary information

Supplementary Figure 1

Phylogenetic relationships of the NA, NP, PA, PB1 and PB2 genes. (PDF 87 kb)

Supplementary Figure 2

Phylogenetic tree of the NS gene. (PDF 80 kb)

Supplementary Figure 3

Location of a potential additional glycosylation site superimposed on the 3D structure of the hemagluttinin molecule. (PDF 73 kb)

Supplementary Table 1

Results of the Ka/Ks rates of substitution analysis for genotype Z viruses. (DOC 52 kb)

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Li, K., Guan, Y., Wang, J. et al. Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia. Nature 430, 209–213 (2004).

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