Kawaguchi Isao, Sasaki Akira, Boots Michael
Department of Biology, Faculty of Science, Kyushu University Graduate Schools, Fukuoka 812-8581, Japan.
Proc Biol Sci. 2003 Nov 7;270(1530):2241-7. doi: 10.1098/rspb.2003.2440.
Dengue virus, the causative agent of dengue fever, has four major serotypes characterized by large genetic and immunological distances. We propose that the unusually large distances between the serotypes can be explained in the light of a process of antibody-dependent enhancement (ADE) leading to increased mortality. Antibody-dependent enhancement results from a new infection with a particular serotype in an individual with acquired immunity to a different serotype. Classical dengue fever causes negligible mortality, but ADE leads to the risk of developing the significantly more dangerous dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS). A mathematical model is presented that describes the epidemiological dynamics of two serotypes of a pathogen where there is the possibility of co-infection and reinfection by a different serotype, along with increased mortality as a result of enhancement. We show that if there is no or slightly increased mortality after reinfection (enhancement), serotypes with a small immunological distance can stably coexist. This suggests that a cloud of serotypes with minor serological differences will constitute the viral population. By contrast, if enhancement is sufficiently great, a substantial immunological distance is necessary for two serotypes to stably coexist in the population. Therefore, high mortality owing to enhancement leads to an evolutionarily stable viral community comprising a set of distantly separated serotypes.
登革热病毒是登革热的病原体，有四种主要血清型，其特点是在基因和免疫方面存在很大差异。我们提出，血清型之间异常大的差异可以根据抗体依赖增强（ADE）过程导致死亡率增加来解释。抗体依赖增强是指个体对一种血清型获得免疫后，又感染了另一种特定血清型。典型的登革热导致的死亡率可忽略不计，但抗体依赖增强会导致出现危险得多的登革出血热（DHF）和登革休克综合征（DSS）的风险。本文提出了一个数学模型，该模型描述了一种病原体两种血清型的流行病学动态，其中存在共同感染和被不同血清型再次感染的可能性，以及由于增强作用导致死亡率增加的情况。我们表明，如果再次感染（增强）后死亡率没有增加或略有增加，免疫距离小的血清型可以稳定共存。这表明血清学差异较小的一群血清型将构成病毒种群。相比之下，如果增强作用足够大，两种血清型要在种群中稳定共存就需要有相当大的免疫距离。因此，由于增强作用导致的高死亡率会导致一个进化上稳定的病毒群落，该群落由一组远距离分离的血清型组成。
