Dynamic effects of anti body-dependent enhancement on the fitness of viruses
Dynamic effects of anti body-dependent enhancement on the fitness of viruses
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DOI：
10.1073/pnas.0507320102
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发表时间：
2005-10-18
影响因子：
11.1
通讯作者：
Burke, DS
中科院分区：
文献类型：
--
作者：
Cummings, DAT;Schwartz, IB;Burke, DS
抗体依赖性增强（ADE）是一种通过免疫血清增加而不是减少病毒复制的现象，已在体外观察到大量具有公共卫生重要性的病毒，包括黄病毒、冠状病毒和逆转录病毒。人体中ADE最显著的体内实例是登革出血热，在这种疾病中，AIDE被认为通过增加病毒复制来增加登革病毒感染的临床表现的严重程度。我们研究了艾滋病对病毒血清型的流行和持久性的流行病学影响。使用一个动力系统模型的n共循环登革热血清型，我们发现，AIDE可以提供一个竞争优势，这些血清型进行增强相比，那些没有，这种优势随着共循环血清型的数量增加。巧合的是，增加ADE水平所提供的选择性优势是有限的，因为更高水平的增强会诱导所有登革热病毒感染发生率的大幅波动，从而威胁到增强型和非增强型血清型的持续存在。虽然这里提出的模型是专门为登革热设计的，我们的研究结果适用于任何流行病学系统，其中部分免疫增加病原体复制率。我们的研究结果表明，增强是最有利的设置中，多个血清型循环，并在一个大的主机人口可用于支持病原体的持久性在深槽的ADE诱导的大幅度振荡的病毒复制。
Antibody-dependent enhancement (ADE), a phenomenon in which viral replication is increased rather than decreased by immune sera, has been observed in vitro for a large number of viruses of public health importance, including flaviviruses, coronaviruses, and retroviruses. The most striking in vivo example of ADE in humans is dengue hemorrhagic fever, a disease in which AIDE is thought to increase the severity of clinical manifestations of dengue virus infection by increasing virus replication. We examine the epidemiological impact of AIDE on the prevalence and persistence of viral serotypes. Using a dynamical system model of n cocirculating dengue serotypes, we find that AIDE may provide a competitive advantage to those serotypes that undergo enhancement compared with those that do not, and that this advantage increases with increasing numbers of cocirculating serotypes. Paradoxically, there are limits to the selective advantage provided by increasing levels of ADE, because greater levels of enhancement induce large amplitude oscillations in incidence of all dengue virus infections, threatening the persistence of both the enhanced and nonenhanced serotypes. Although the models presented here are specifically designed for dengue, our results are applicable to any epidemiological system in which partial immunity increases pathogen replication rates. Our results suggest that enhancement is most advantageous in settings where multiple serotypes circulate and where a large host population is available to support pathogen persistence during the deep troughs of ADE-induced large amplitude oscillations of virus replication.