Department of Ecology and Evolution, University of Chicago, Chicago, Illinois, United States of America.
Department of Science, Technology, and Society, York University, Toronto, Canada.
PLoS Biol. 2023 Sep 7;21(9):e3002268. doi: 10.1371/journal.pbio.3002268. eCollection 2023 Sep.
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.
未来大流行病风险的管理需要更好地了解决定新发人畜共患病病毒毒力的机制。荟萃分析表明，新发人畜共患病的毒力与储主宿主系统发育相关，但不能完全从其系统发育中预测，这表明储主宿主免疫学和生活史的具体特征可能推动了负责跨物种毒力的病毒特征的进化。特别是，蝙蝠宿主的病毒在溢出到人类时导致的病死率高于从任何其他哺乳动物中获得的病毒，这种现象不能仅用系统发育距离来解释。为了理清这些模式的基本驱动因素，我们开发了一个嵌套建模框架，该框架突出了在引起跨物种出现后毒力的储主宿主中支撑病毒特征进化的机制。我们将该框架应用于从各种哺乳动物储主中衍生的病毒人畜共患病的毒力预测，重现了文献中报道的病毒引起人类死亡率的趋势。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高毒力，更普遍地，展示了储主宿主寿命、病毒耐受性和组成性免疫方面的关键差异如何影响引起跨物种毒力的病毒特征的进化溢出到人类后。我们的理论框架提供了一系列可检验的问题和预测，旨在激发未来比较源自不同哺乳动物宿主的人畜共患病病毒跨物种毒力进化的工作。
