Viral and Epidemiological Determinants of the Invasion Dynamics of Novel Dengue Genotypes

Figure included in the study "Viral and Epidemiological Determinants of the Invasion Dynamics of Novel Dengue Genotypes" in PLoS NTD, 2010. Abstract: "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. 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. 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."

本数据图来自2010年发表于《PLOS 被忽视热带病》（PLoS Neglected Tropical Diseases, PLoS NTD）的研究"新型登革热基因型入侵动态的病毒学与流行病学决定因素"。摘要：登革热已成为全球公共卫生领域的重大关切问题。频繁暴发的疫情被认为是由其四种共同流行血清型之间复杂的免疫学相互作用，以及蚊虫密度的大幅波动共同驱动的。由不同程度的交叉保护或病毒适配性差异引发的病毒谱系替换事件，也与登革热流行病学的暂时性改变相关。近期在东南亚地区曾报道过一次重大替换事件：登革热2型病毒的亚洲-1基因型取代了当地流行的亚洲/美洲型毒株。尽管该事件被认为是由于病毒在人-蚊传播能力提升方面的适配性增强所致，但并未观察到登革热流行病学特征出现显著变化。本研究通过模型系统探究新型优势登革热基因型的入侵动态，明确影响其成功定植与固定速率的相关因素，以及该过程带来的流行病学后果。研究结果显示，尽管病毒适配性总体上与入侵成功及对本土基因型的竞争性排斥相关，但流行病学环境对新型基因型的成功定植起到更为关键的作用。因此，若新型基因型在登革热高流行时段（尤其是针对该特定血清型的流行期）被引入，即便具备适配性优势，仍可能面临较高的随机灭绝风险。登革热正选择标记的稀缺性，常被归因于强烈的纯化选择：登革热的双宿主循环所施加的选择约束，预计会导致较高的有害突变率。本研究结果表明，即便具备极高适配优势的突变株也面临严重的灭绝威胁，这意味着除纯化选择外，季节性瓶颈效应之外的随机效应与遗传漂变，在塑造登革热病毒的生态学与进化过程中同样发挥着重要作用。