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. 2010 Jan 8;5(1):e8631.
doi: 10.1371/journal.pone.0008631.

Spatiotemporal structure of molecular evolution of H5N1 highly pathogenic avian influenza viruses in Vietnam

Margaret A Carrel  1 , Michael Emch, R Todd Jobe, Aaron Moody, Xiu-Feng Wan
Affiliations

Spatiotemporal structure of molecular evolution of H5N1 highly pathogenic avian influenza viruses in Vietnam

Margaret A Carrel et al. PLoS One. .

Abstract

Background: 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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Genetic versus geographic distance of HK821-like HPAIVs in Vietnam.
The least squares line is plotted in grey.
Figure 2
Figure 2. Genetic versus geographic distance of HK821-like HPAIVs, stratified by year and gene segment.
Figure 3
Figure 3. Boxplots of genetic versus geographic distance for the within- and between-region pairs of H5N1 HPAIVs in Vietnam.
The solid black circle is the median genetic distance in each grouping. Hollow circles represent outliers.
Figure 4
Figure 4. Mantel spatial correlograms, stratified by influenza gene segment.
Correlograms show the relationship between geographic distance (x-axis) and the Mantel r correlation score (y-axis) of HK821-like HPAIVs. Under the null hypothesis of no relationship between geographic location and genetic similarity, all points would be on the zero line. Points above the zero line indicate lower genetic distance between case pairs. Points below the zero line indicate greater genetic distance between case pairs. Solid symbols are statistically significant, hollow symbols are not. The sharp rise to the furthest point in the correlograms is an artifact of edge effects caused by the spatial structure of the data, and does not indicate genetic similarity at the highest geographic distances between viruses.
Figure 5
Figure 5. Geographic distribution of H5N1 highly pathogenic avian influenza viruses (HPAIVs) used in this study.
Darkened provinces indicate locations of virus isolation.
See this image and copyright information in PMC

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