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.
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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)