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. 2006 Feb 21;103(8):2845-50.
doi: 10.1073/pnas.0511120103. Epub 2006 Feb 10.

Establishment of multiple sublineages of H5N1 influenza virus in Asia: implications for pandemic control

H Chen  1 , G J D Smith, K S Li, J Wang, X H Fan, J M Rayner, D Vijaykrishna, J X Zhang, L J Zhang, C T Guo, C L Cheung, K M Xu, L Duan, K Huang, K Qin, Y H C Leung, W L Wu, H R Lu, Y Chen, N S Xia, T S P Naipospos, K Y Yuen, S S Hassan, S Bahri, T D Nguyen, R G Webster, J S M Peiris, Y Guan
Affiliations

Establishment of multiple sublineages of H5N1 influenza virus in Asia: implications for pandemic control

H Chen et al. Proc Natl Acad Sci U S A. .

Abstract

Preparedness for a possible influenza pandemic caused by highly pathogenic avian influenza A subtype H5N1 has become a global priority. The spread of the virus to Europe and continued human infection in Southeast Asia have heightened pandemic concern. It remains unknown from where the pandemic strain may emerge; current attention is directed at Vietnam, Thailand, and, more recently, Indonesia and China. Here, we report that genetically and antigenically distinct sublineages of H5N1 virus have become established in poultry in different geographical regions of Southeast Asia, indicating the long-term endemicity of the virus, and the isolation of H5N1 virus from apparently healthy migratory birds in southern China. Our data show that H5N1 influenza virus, has continued to spread from its established source in southern China to other regions through transport of poultry and bird migration. The identification of regionally distinct sublineages contributes to the understanding of the mechanism for the perpetuation and spread of H5N1, providing information that is directly relevant to control of the source of infection in poultry. It points to the necessity of surveillance that is geographically broader than previously supposed and that includes H5N1 viruses of greater genetic and antigenic diversity.

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Conflict of interest statement

Conflict of interest statement: No conflicts declared.

Figures

Fig. 1.
Fig. 1.
Map of eastern Asia showing Fujian, Guangdong, Guangxi, Guizhou, Hong Kong, Hunan, and Yunnan where influenza surveillance was conducted and the locations of Poyang and Qinghai Lakes. Following are the genotypes of H5N1 viruses tested in poultry from each Province in our surveillance program in southern China since 2004, plus data from migratory birds at Poyang and Qinghai Lakes: Guangxi, genotypes W (15), Z (5), and G (3); Hunan, genotypes Z (13) and G (3); Fujian, genotype Z (2); Yunnan, genotype Z (4); Guangdong, genotype Z (7); Poyang Lake, genotypes Z (3) and V (3); Qinghai Lake, genotype Z (20). (Scale bar: 500 km.)
Fig. 2.
Fig. 2.
Phylogenetic relationships of the HA (A) and NP (B) genes of representative influenza A viruses isolated in Asia. Trees were generated by the neighbor-joining method in the paup* program (35) (maximum-likelihood and Bayesian analysis revealed the same relationships). Numbers above and below branches indicate neighbor-joining bootstrap values and Bayesian posterior probabilities. Not all supports are shown due to space constraints. Analysis was based on nucleotides 1–1696 of the HA gene and 1–990 of the NP gene. The HA tree was rooted to Gs/GD/1/96 and the NP tree to Dk/HK/Y280/97. (Scale bar: 0.01 substitutions per site.) Purple, viruses from Indonesia; red, viruses from Vietnam, Thailand, and Malaysia; green (genotype V) and blue (genotype Z), viruses isolated from migratory birds; brown, viruses isolated from poultry in Hunan and Yunnan in late 2004 and early 2005. GD, Guangdong; HN, Hunan; IDN, Indonesia; MB, migratory bird; YN, Yunnan; VNM2, recent Vietnam introduction; VTM, Vietnam/Thailand/Malaysia. ∗, Because 90% of the poultry consumed in Hong Kong was imported from Guangdong, the viruses isolated from domestic and migratory birds in Hong Kong were designated as belonging to the GD sublineage.
Fig. 3.
Fig. 3.
Genotypes of H5N1 influenza reassortants in Asia. The eight gene segments are (horizontal bars starting at the top downward): PB2, PB1, PA, HA, NP, NA, M, and NS. Each color represents a virus lineage, with red indicating origin from Gs/GD/1/96. The definition of genotypes and the generation of genotypes Z, Z+, V, and W have been described (13). Novel genotype G seems to have resulted from reassortment between genotypes Z and W circulating in southern China.
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