Department of Geography, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA.
PLoS One. 2010 Jan 8;5(1):e8631. doi: 10.1371/journal.pone.0008631.
Vietnam is one of the countries most affected by outbreaks of H5N1 highly pathogenic avian influenza viruses. First identified in Vietnam in poultry in 2001 and in humans in 2004, the virus has since caused 111 cases and 56 deaths in humans. In 2003/2004 H5N1 outbreaks, nearly the entire poultry population of Vietnam was culled. Our earlier study (Wan et al., 2008, PLoS ONE, 3(10): e3462) demonstrated that there have been at least six independent H5N1 introductions into Vietnam and there were nine newly emerged reassortants from 2001 to 2007 in Vietnam. H5N1 viruses in Vietnam cluster distinctly around Hanoi and Ho Chi Minh City. However, the nature of the relationship between genetic divergence and geographic patterns is still unclear.
METHODOLOGY/PRINCIPAL FINDINGS: In this study, we hypothesized that genetic distances between H5N1 viruses in Vietnam are correlated with geographic distances, as the result of distinct population and environment patterns along Vietnam's long north to south longitudinal extent. Based on this hypothesis, we combined spatial statistical methods with genetic analytic techniques and explicitly used geographic space to explore genetic evolution of H5N1 highly pathogenic avian influenza viruses at the sub-national scale in Vietnam. Our dataset consisted of 125 influenza viruses (with whole genome sets) isolated in Vietnam from 2003 to 2007. Our results document the significant effect of space and time on genetic evolution and the rise of two regional centers of genetic mixing by 2007. These findings give insight into processes underlying viral evolution and suggest that genetic differentiation is associated with the distance between concentrations of human and poultry populations around Hanoi and Ho Chi Minh City.
CONCLUSIONS/SIGNIFICANCE: The results show that genetic evolution of H5N1 viruses in Vietnamese domestic poultry is highly correlated with the location and spread of those viruses in geographic space. This correlation varies by scale, time, and gene, though a classic isolation by distance pattern is observed. This study is the first to characterize the geographic structure of influenza viral evolution at the sub-national scale in Vietnam and can shed light on how H5N1 HPAIVs evolve in certain geographic settings.
越南是受 H5N1 高致病性禽流感病毒爆发影响最严重的国家之一。该病毒于 2001 年在越南家禽中首次被发现，2004 年在人类中被发现，此后已导致 111 例人类感染和 56 人死亡。在 2003/2004 年的 H5N1 爆发中，越南几乎全部家禽都被扑杀。我们之前的研究（Wan 等人，2008 年，PLoS ONE，3（10）：e3462）表明，至少有 6 次 H5N1 独立传入越南，2001 年至 2007 年期间，越南有 9 种新出现的重组体。越南的 H5N1 病毒明显围绕着河内和胡志明市聚集。然而，遗传分化与地理模式之间的关系性质仍不清楚。
方法/主要发现：在这项研究中，我们假设越南的 H5N1 病毒之间的遗传距离与地理距离相关，这是由于越南从北到南的漫长纵向延伸导致的独特的种群和环境模式的结果。基于这一假设，我们结合空间统计方法和遗传分析技术，并明确使用地理空间来探索越南次国家尺度 H5N1 高致病性禽流感病毒的遗传进化。我们的数据集包括 2003 年至 2007 年在越南分离的 125 株流感病毒（具有全基因组集）。我们的研究结果记录了空间和时间对遗传进化的显著影响，并记录了 2007 年两个区域遗传混合中心的兴起。这些发现深入了解了病毒进化的过程，并表明遗传分化与河内和胡志明市周围人口和家禽种群的浓度之间的距离有关。
结论/意义：研究结果表明，越南国内家禽中 H5N1 病毒的遗传进化与这些病毒在地理空间中的位置和传播高度相关。这种相关性因规模、时间和基因而异，但观察到了经典的隔离距离模式。这项研究首次描述了越南次国家尺度流感病毒进化的地理结构，并可以揭示 H5N1 HPAIV 在某些地理环境中的进化方式。
