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Global and Local Persistence of Influenza A(H5N1) Virus - Volume 20, Number 8—August 2014 - Emerging Infectious Disease journal - CDC

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Global and Local Persistence of Influenza A(H5N1) Virus - Volume 20, Number 8—August 2014 - Emerging Infectious Disease journal - CDC

Volume 20, Number 8—August 2014


Global and Local Persistence of Influenza A(H5N1) Virus

Xianbin Li, Zhong Zhang, Ailian Yu, Simon Y. W. Ho, Michael J. Carr, Weimin Zheng, Yanzhou Zhang, Chaodong Zhu1, Fumin Lei1, and Weifeng Shi1Comments to Author 
Author affiliations: Chinese Academy of Sciences, Shenzhen, China (X. Li)Taishan Medical College, Taian, Shandong, China (Z. Zhang, A. Yu, W. Shi)Chinese Academy of Sciences, Beijing, China (X. Li, W. Zheng, Y. Zhang, C. Zhu, F. Lei)University of Sydney, Sydney, New South Wales, Australia (S.Y.W. Ho)University College Dublin, Dublin, Ireland (M.J. Carr)1These authors contributed equally to this article.


An understanding of the global migration dynamics of highly pathogenic avian influenza A(H5N1) virus is helpful for surveillance and disease prevention. To characterize the migration network of this virus, we used genetic analysis, which supported a global persistence model in which each of 9 regions acts to some extent as a source. Siberia is the major hub for the dispersal of the virus. Southeast Asia and Africa are major sources of genetically and antigenically novel strains. We found evidence of local persistence of the virus in Southeast Asia and Africa, which is rare for human influenza A viruses. The differences in migration dynamics between avian and human influenza viruses might help with the design of region-specific surveillance efforts and the selection of vaccine candidates.
Highly pathogenic avian influenza (HPAI) A(H5N1) virus is an ineradicable zoonotic virus that continues to mutate and reassort in nature and poses a serious threat to avian and human health. As the natural hosts of avian influenza viruses, wild birds are the main reservoir for the HPAI (H5N1) pandemic; whether these birds contribute to the viruses’ global circulation remains under debate (13).
Since their emergence in China in 1996 (4), HPAI (H5N1) viruses have spread to most Eurasian and African countries and have caused 650 laboratory-confirmed cases of human infection and 386 deaths (5). Understanding the migration dynamics of HPAI (H5N1) viruses is thus essential for surveillance and prevention of these infections in birds and humans and for policy decisions on vaccine development and/or implementation.
Numerous genetic studies have been conducted to determine the mechanisms underlying influenza A virus seasonality among humans; most results support a model of global migration (611). Rambaut et al. proposed a source–sink model for virus ecology (7), in which the tropics are the source regions and the subtropical and temperate zones of the Northern and Southern Hemispheres are the sink regions. Similarly, Russell et al. suggested that eastern and Southeast Asia comprise a regional circulation network that is the leading region for the evolution of human influenza viruses (8). However, Bedford et al. found that seasonal epidemics in the United States had seeded epidemics around the world in a pattern called global persistence (9). More recently, Bahl et al. found that the tropics (e.g., Southeast Asia and Hong Kong) did not maintain a source for annual epidemics of influenza A(H3N2) virus infection (12). Alternatively, each geographic region might act as a potential source, supporting the global persistence model.
Also extensively studied have been the migration mechanisms of avian influenza A(H5N1) virus (1315). Despite the use of different methods, many studies reached the same conclusion: China is the source of multiple clusters of influenza A(H5N1) viruses identified from other countries in eastern and Southeast Asia (1318). Liang et al. have also proposed that southern China and Southeast Asia might be the source of influenza A(H5N1) virus, seeding outbreaks elsewhere, and that eastern Siberia might be the source of influenza A(H5N1) virus cross-infection and genetic reassortment (19).
However, several questions remain with regard to the migration of HPAI (H5N1) viruses. For example, what are the features of their global migration network? Which region acts as the key node? Is southern China the only source of novel HPAI (H5N1) viruses? If not, what are the other sources? Are the sources stable, or do their contributions change with time?
To address these questions, we analyzed a large number of hemagglutinin gene sequences of influenza A(H5N1) viruses from avian hosts by using BEAST (20) and Migrate (21,22), which can estimate genetic diversity of each region and migration rates between regions. On the basis of these findings, we characterized the global migration network and studied the migratory mechanism of HPAI (H5N1) viruses.

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