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Viral and epidemiological determinants of the invasion dynamics of novel dengue genotypes.

Lourenço J, Recker M - PLoS Negl Trop Dis (2010)

Bottom Line: Frequent epidemic outbreaks are believed to be driven by a complex interplay of immunological interactions between its four co-circulating serotypes and large fluctuations in mosquito densities.The rarity of markers for positive selection has often been explained by strong purifying selection whereby the constraints imposed by dengue's two-host cycle are expected to result in a high rate of deleterious mutations.Our results demonstrate that even highly beneficial mutants are under severe threat of extinction, which would suggest that apart from purifying selection, stochastic effects and genetic drift beyond seasonal bottlenecks are equally important in shaping dengue's viral ecology and evolution.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, University of Oxford, Oxford, United Kingdom.

ABSTRACT

Background: Dengue has become a major concern for international public health. Frequent epidemic outbreaks are believed to be driven by a complex interplay of immunological interactions between its four co-circulating serotypes and large fluctuations in mosquito densities. Viral lineage replacement events, caused for example by different levels of cross-protection or differences in viral fitness, have also been linked to a temporary change in dengue epidemiology. A major replacement event was recently described for South-East Asia where the Asian-1 genotype of dengue serotype 2 replaced the resident Asian/American type. Although this was proposed to be due to increased viral fitness in terms of enhanced human-to-mosquito transmission, no major change in dengue epidemiology could be observed.

Methods/results: Here we investigate the invasion dynamics of a novel, advantageous dengue genotype within a model system and determine the factors influencing the success and rate of fixation as well as their epidemiological consequences. We find that while viral fitness overall correlates with invasion success and competitive exclusion of the resident genotype, the epidemiological landscape plays a more significant role for successful emergence. Novel genotypes can thus face high risks of stochastic extinction despite their fitness advantage if they get introduced during episodes of high dengue prevalence, especially with respect to that particular serotype.

Conclusion: The rarity of markers for positive selection has often been explained by strong purifying selection whereby the constraints imposed by dengue's two-host cycle are expected to result in a high rate of deleterious mutations. Our results demonstrate that even highly beneficial mutants are under severe threat of extinction, which would suggest that apart from purifying selection, stochastic effects and genetic drift beyond seasonal bottlenecks are equally important in shaping dengue's viral ecology and evolution.

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Related in: MedlinePlus

The effect of transmission and serotype competition on invasion success.The success rate of the invading genotype, DENV2′, strongly varies depending on the number of total infected individuals and the relative prevalence of serotype 2 in the population at the time point of introduction (TPI). (A) The invasion success (orange line) oscillates out of phase with total dengue incidence (grey line) and is minimized when disease prevalence peaks, demonstrating how the current level of transmission can influence the invasion success of new advantageous genotypes. (B) The highest rates of successful invasions can be observed during periods of low relative prevalence of serotype 2 (blue line). In contrast, the probability of an invading advantageous genotype to get established and reach fixation is significantly reduced as serotype 2 gains wide-spread dominant within the population. Parameters as in Table 1 and .
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pntd-0000894-g006: The effect of transmission and serotype competition on invasion success.The success rate of the invading genotype, DENV2′, strongly varies depending on the number of total infected individuals and the relative prevalence of serotype 2 in the population at the time point of introduction (TPI). (A) The invasion success (orange line) oscillates out of phase with total dengue incidence (grey line) and is minimized when disease prevalence peaks, demonstrating how the current level of transmission can influence the invasion success of new advantageous genotypes. (B) The highest rates of successful invasions can be observed during periods of low relative prevalence of serotype 2 (blue line). In contrast, the probability of an invading advantageous genotype to get established and reach fixation is significantly reduced as serotype 2 gains wide-spread dominant within the population. Parameters as in Table 1 and .

Mentions: The results from our deterministic model suggest that novel genotypes can face long periods at very low prevalence before breaching a detection threshold and going to fixation. Within a more realistic setting these periods signify an enhanced risk of stochastic extinction of the novel type despite its fitness advantage over the resident type. To better address the invasion success of DENV2′ we used a stochastic formulation of our model (see Methods) and simulated a number of invasion events over a period of four years and recorded the success rate of invasion, here defined as the successful introduction into a population followed by competitive exclusion of the resident type. As demonstrated in Figure 6A we observed that invasion success shows an oscillatory behaviour whose phase seems negatively correlated to total dengue prevalence at time of introduction. This suggests that the invasion of a newly advantageous genotype can be hampered by serotype competition during epidemics and favoured during off-season periods. Moreover, the amplitude of oscillation, i.e. the maximum success rate, is dependent on and again negatively correlated to serotype 2 prevalence. Figure 6B shows the increase in relative prevalence of DENV2 over the 4-year period which clearly correlates with a decline in the success rate of DENV2′.


Viral and epidemiological determinants of the invasion dynamics of novel dengue genotypes.

Lourenço J, Recker M - PLoS Negl Trop Dis (2010)

The effect of transmission and serotype competition on invasion success.The success rate of the invading genotype, DENV2′, strongly varies depending on the number of total infected individuals and the relative prevalence of serotype 2 in the population at the time point of introduction (TPI). (A) The invasion success (orange line) oscillates out of phase with total dengue incidence (grey line) and is minimized when disease prevalence peaks, demonstrating how the current level of transmission can influence the invasion success of new advantageous genotypes. (B) The highest rates of successful invasions can be observed during periods of low relative prevalence of serotype 2 (blue line). In contrast, the probability of an invading advantageous genotype to get established and reach fixation is significantly reduced as serotype 2 gains wide-spread dominant within the population. Parameters as in Table 1 and .
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2990689&req=5

pntd-0000894-g006: The effect of transmission and serotype competition on invasion success.The success rate of the invading genotype, DENV2′, strongly varies depending on the number of total infected individuals and the relative prevalence of serotype 2 in the population at the time point of introduction (TPI). (A) The invasion success (orange line) oscillates out of phase with total dengue incidence (grey line) and is minimized when disease prevalence peaks, demonstrating how the current level of transmission can influence the invasion success of new advantageous genotypes. (B) The highest rates of successful invasions can be observed during periods of low relative prevalence of serotype 2 (blue line). In contrast, the probability of an invading advantageous genotype to get established and reach fixation is significantly reduced as serotype 2 gains wide-spread dominant within the population. Parameters as in Table 1 and .
Mentions: The results from our deterministic model suggest that novel genotypes can face long periods at very low prevalence before breaching a detection threshold and going to fixation. Within a more realistic setting these periods signify an enhanced risk of stochastic extinction of the novel type despite its fitness advantage over the resident type. To better address the invasion success of DENV2′ we used a stochastic formulation of our model (see Methods) and simulated a number of invasion events over a period of four years and recorded the success rate of invasion, here defined as the successful introduction into a population followed by competitive exclusion of the resident type. As demonstrated in Figure 6A we observed that invasion success shows an oscillatory behaviour whose phase seems negatively correlated to total dengue prevalence at time of introduction. This suggests that the invasion of a newly advantageous genotype can be hampered by serotype competition during epidemics and favoured during off-season periods. Moreover, the amplitude of oscillation, i.e. the maximum success rate, is dependent on and again negatively correlated to serotype 2 prevalence. Figure 6B shows the increase in relative prevalence of DENV2 over the 4-year period which clearly correlates with a decline in the success rate of DENV2′.

Bottom Line: Frequent epidemic outbreaks are believed to be driven by a complex interplay of immunological interactions between its four co-circulating serotypes and large fluctuations in mosquito densities.The rarity of markers for positive selection has often been explained by strong purifying selection whereby the constraints imposed by dengue's two-host cycle are expected to result in a high rate of deleterious mutations.Our results demonstrate that even highly beneficial mutants are under severe threat of extinction, which would suggest that apart from purifying selection, stochastic effects and genetic drift beyond seasonal bottlenecks are equally important in shaping dengue's viral ecology and evolution.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, University of Oxford, Oxford, United Kingdom.

ABSTRACT

Background: Dengue has become a major concern for international public health. Frequent epidemic outbreaks are believed to be driven by a complex interplay of immunological interactions between its four co-circulating serotypes and large fluctuations in mosquito densities. Viral lineage replacement events, caused for example by different levels of cross-protection or differences in viral fitness, have also been linked to a temporary change in dengue epidemiology. A major replacement event was recently described for South-East Asia where the Asian-1 genotype of dengue serotype 2 replaced the resident Asian/American type. Although this was proposed to be due to increased viral fitness in terms of enhanced human-to-mosquito transmission, no major change in dengue epidemiology could be observed.

Methods/results: Here we investigate the invasion dynamics of a novel, advantageous dengue genotype within a model system and determine the factors influencing the success and rate of fixation as well as their epidemiological consequences. We find that while viral fitness overall correlates with invasion success and competitive exclusion of the resident genotype, the epidemiological landscape plays a more significant role for successful emergence. Novel genotypes can thus face high risks of stochastic extinction despite their fitness advantage if they get introduced during episodes of high dengue prevalence, especially with respect to that particular serotype.

Conclusion: The rarity of markers for positive selection has often been explained by strong purifying selection whereby the constraints imposed by dengue's two-host cycle are expected to result in a high rate of deleterious mutations. Our results demonstrate that even highly beneficial mutants are under severe threat of extinction, which would suggest that apart from purifying selection, stochastic effects and genetic drift beyond seasonal bottlenecks are equally important in shaping dengue's viral ecology and evolution.

Show MeSH
Related in: MedlinePlus