Evolutionary Dynamics and Emergence of Panzootic H5N1 Influenza Viruses

PLoS Pathogens, Sep 2008

The highly pathogenic avian influenza (HPAI) H5N1 virus lineage has undergone extensive genetic reassortment with viruses from different sources to produce numerous H5N1 genotypes, and also developed into multiple genetically distinct sublineages in China. From there, the virus has spread to over 60 countries. The ecological success of this virus in diverse species of both poultry and wild birds with frequent introduction to humans suggests that it is a likely source of the next human pandemic. Therefore, the evolutionary and ecological characteristics of its emergence from wild birds into poultry are of considerable interest. Here, we apply the latest analytical techniques to infer the early evolutionary dynamics of H5N1 virus in the population from which it emerged (wild birds and domestic poultry). By estimating the time of most recent common ancestors of each gene segment, we show that the H5N1 prototype virus was likely introduced from wild birds into poultry as a non-reassortant low pathogenic avian influenza H5N1 virus and was not generated by reassortment in poultry. In contrast, more recent H5N1 genotypes were generated locally in aquatic poultry after the prototype virus (A/goose/Guangdong/1/96) introduction occurred, i.e., they were not a result of additional emergence from wild birds. We show that the H5N1 virus was introduced into Indonesia and Vietnam 3–6 months prior to detection of the first outbreaks in those countries. Population dynamics analyses revealed a rapid increase in the genetic diversity of A/goose/Guangdong/1/96 lineage viruses from mid-1999 to early 2000. Our results suggest that the transmission of reassortant viruses through the mixed poultry population in farms and markets in China has selected HPAI H5N1 viruses that are well adapted to multiple hosts and reduced the interspecies transmission barrier of those viruses.

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Evolutionary Dynamics and Emergence of Panzootic H5N1 Influenza Viruses

et al. (2008) Evolutionary Dynamics and Emergence of Panzootic H5N1 Influenza Viruses. PLoS Pathog 4(9): e1000161. doi:10.1371/journal.ppat.1000161 Evolutionary Dynamics and Emergence of Panzootic H5N1 Influenza Viruses Dhanasekaran Vijaykrishna Justin Bahl Steven Riley Lian Duan Jin Xia Zhang Honglin Chen J. S. Malik Peiris Gavin J. D. Smith Yi Guan Ron A. M. Fouchier, Erasmus Medical Center, The Netherlands The highly pathogenic avian influenza (HPAI) H5N1 virus lineage has undergone extensive genetic reassortment with viruses from different sources to produce numerous H5N1 genotypes, and also developed into multiple genetically distinct sublineages in China. From there, the virus has spread to over 60 countries. The ecological success of this virus in diverse species of both poultry and wild birds with frequent introduction to humans suggests that it is a likely source of the next human pandemic. Therefore, the evolutionary and ecological characteristics of its emergence from wild birds into poultry are of considerable interest. Here, we apply the latest analytical techniques to infer the early evolutionary dynamics of H5N1 virus in the population from which it emerged (wild birds and domestic poultry). By estimating the time of most recent common ancestors of each gene segment, we show that the H5N1 prototype virus was likely introduced from wild birds into poultry as a non-reassortant low pathogenic avian influenza H5N1 virus and was not generated by reassortment in poultry. In contrast, more recent H5N1 genotypes were generated locally in aquatic poultry after the prototype virus (A/ goose/Guangdong/1/96) introduction occurred, i.e., they were not a result of additional emergence from wild birds. We show that the H5N1 virus was introduced into Indonesia and Vietnam 3-6 months prior to detection of the first outbreaks in those countries. Population dynamics analyses revealed a rapid increase in the genetic diversity of A/goose/Guangdong/ 1/96 lineage viruses from mid-1999 to early 2000. Our results suggest that the transmission of reassortant viruses through the mixed poultry population in farms and markets in China has selected HPAI H5N1 viruses that are well adapted to multiple hosts and reduced the interspecies transmission barrier of those viruses. - Funding: This study was supported by the Li Ka Shing Foundation, the National Institutes of Health (NIAID contract HHSN266200700005C), the Area of Excellence Scheme of the University Grants Committee (Grant AoE/M-12/06) and Research Grants Council (HKU 7512/06 M) of the Hong Kong SAR Government. GJDS is supported by a career development award under NIAID contract HHSN266200700005C. Competing Interests: The authors have declared that no competing interests exist. Outbreaks of highly pathogenic avian influenza (HPAI) H5N1 virus were first recorded in Guangdong, China in 1996 [1]. Since its emergence, the A/goose/Guangdong/1/96 (Gs/GD) virus lineage has become the longest recorded HPAI virus to remain endemic in poultry [2]. The ecological success of this virus in diverse avian and mammalian species [3] with frequent introduction to humans suggests this virus is the most likely candidate of the next human pandemic [4]. Therefore, the evolutionary and ecological characteristics of its emergence from wild birds into poultry are of considerable interest. The virus gradually became endemic in poultry in different regions of China, developing into genetically and antigenically distinct sublineages [5,6]. The geographic spread of these sublineages outside China is also unprecedented, with two sublineages spreading to Southeast Asia in late 2003, and another westwards to Central Asia, Europe, Africa, the Middle East and the Indian subcontinent in mid-2005 [1,59]. During mid-2005, one sublineage (Fujian-like or clade 2.3.4) became dominant in China and subsequently spread to Laos, Thailand and Vietnam [2,10]. Influenza surveillance in southern China has revealed that the Gs/GD virus lineage underwent extensive genetic reassortment to generate many different reassortant viruses (or genotypes) between 1997 and 2006 [5,6]. The non-reassortant Gs/GD-like viruses were prevalent only from 1996 to 2000 [11]. Afterwards, all H5N1 viruses detected were reassortant genotypes. Amongst all recognized reassortants, only genotypes B, X0, W, Z, G and V, were persistent for more than two years or predominant at different time points, while many genotypes were only detected occasionally [5,6]. While the genetic and antigenic evolution and geographic spread of the HPAI H5N1 panzootic viruses are well documented after the initiation of systematic surveillance in 2000 [5], little is known about the source and early evolutionary dynamics of H5N1 virus. In particular, it is still unknown whether the Gs/GD virus itself was a reassortant virus or introduced wholly from migratory waterfowl. Even though the internal gene sources for most genotypes have been identified from aqua (...truncated)


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Dhanasekaran Vijaykrishna, Justin Bahl, Steven Riley, Lian Duan, Jin Xia Zhang, Honglin Chen, J. S. Malik Peiris, Gavin J. D. Smith, Yi Guan. Evolutionary Dynamics and Emergence of Panzootic H5N1 Influenza Viruses, PLoS Pathogens, 2008, Volume 4, Issue 9, DOI: 10.1371/journal.ppat.1000161