Reservoir host immunology and life history shape virulence evolution in zoonotic viruses.
Reservoir host immunology and life history shape virulence evolution in zoonotic viruses.
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DOI：
10.1371/journal.pbio.3002268
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发表时间：
2023-09
期刊：
影响因子：
9.8
通讯作者：
中科院分区：
文献类型：
--
作者：
未来大流行风险的管理需要更好地了解决定新出现的人畜共患病病毒毒力的机制。荟萃分析表明，新出现的人畜共患病的毒力相关，但不能完全预测从水库宿主的遗传，这表明水库宿主的免疫学和生活史的具体特点可能会推动负责跨物种毒力的病毒性状的演变。特别是，蝙蝠携带的病毒在传播给人类时造成的病死率比来自任何其他哺乳动物的病毒都高，这一现象不能仅用系统发育距离来解释。为了解开这些模式的基本驱动因素，我们开发了一个嵌套的建模框架，突出强调机制，支持水库主机的病毒性状的演变，导致毒力后，跨物种出现。我们应用这个框架来产生来自不同哺乳动物宿主的病毒性人畜共患病的毒力预测，重新捕获文献中报道的病毒引起的人类死亡率的趋势。值得注意的是，我们的工作提供了一个机制假说来解释蝙蝠传播的人畜共患病的极端毒力，更一般地说，证明了储存宿主寿命，病毒耐受性和组成性免疫力的关键差异如何影响病毒特征的演变，这些特征会导致毒力溢出到人类。我们的理论框架提供了一系列可测试的问题和预测，旨在刺激未来的工作比较跨物种的毒力进化的人畜共患病病毒来自不同的哺乳动物宿主。蝙蝠是病毒的天然储存宿主，与其他来源的人畜共患病相比，这些病毒在人类中造成的病死率更高。本研究建立了一个嵌套的宿主内、种群水平的模型，为这一现象提供了一个机制性的解释。
The management of future pandemic risk requires a better understanding of the mechanisms that determine the virulence of emerging zoonotic viruses. Meta-analyses suggest that the virulence of emerging zoonoses is correlated with but not completely predictable from reservoir host phylogeny, indicating that specific characteristics of reservoir host immunology and life history may drive the evolution of viral traits responsible for cross-species virulence. In particular, bats host viruses that cause higher case fatality rates upon spillover to humans than those derived from any other mammal, a phenomenon that cannot be explained by phylogenetic distance alone. In order to disentangle the fundamental drivers of these patterns, we develop a nested modeling framework that highlights mechanisms that underpin the evolution of viral traits in reservoir hosts that cause virulence following cross-species emergence. We apply this framework to generate virulence predictions for viral zoonoses derived from diverse mammalian reservoirs, recapturing trends in virus-induced human mortality rates reported in the literature. Notably, our work offers a mechanistic hypothesis to explain the extreme virulence of bat-borne zoonoses and, more generally, demonstrates how key differences in reservoir host longevity, viral tolerance, and constitutive immunity impact the evolution of viral traits that cause virulence following spillover to humans. Our theoretical framework offers a series of testable questions and predictions designed to stimulate future work comparing cross-species virulence evolution in zoonotic viruses derived from diverse mammalian hosts. Bats are natural reservoir hosts for viruses that cause higher case fatality rates in humans than do zoonoses derived from any other source. This study builds a nested within-host, population-level model to offer a mechanistic explanation for this phenomenon.