Department of Integrative Biology, University of California, Berkeley, Berkeley, United States.
Department of Ecology and Evolutionary Biology, Princeton University, Princeton, United States.
Elife. 2020 Feb 3;9:e48401. doi: 10.7554/eLife.48401.
Bats host virulent zoonotic viruses without experiencing disease. A mechanistic understanding of the impact of bats' virus hosting capacities, including uniquely constitutive immune pathways, on cellular-scale viral dynamics is needed to elucidate zoonotic emergence. We carried out virus infectivity assays on bat cell lines expressing induced and constitutive immune phenotypes, then developed a theoretical model of our system, which we fit to empirical data. Best fit models recapitulated expected immune phenotypes for representative cell lines, supporting robust antiviral defenses in bat cells that correlated with higher estimates for within-host viral propagation rates. In general, heightened immune responses limit pathogen-induced cellular morbidity, which can facilitate the establishment of rapidly-propagating persistent infections within-host. Rapidly-transmitting viruses that have evolved with bat immune systems will likely cause enhanced virulence following emergence into secondary hosts with immune systems that diverge from those unique to bats.
蝙蝠携带致命的人畜共患病病毒而不发病。为了阐明人畜共患病的出现,需要从细胞尺度的病毒动力学方面,了解蝙蝠的病毒携带能力(包括独特的固有免疫途径)对病毒的影响。我们对表达诱导和固有免疫表型的蝙蝠细胞系进行了病毒感染力测定,然后开发了我们系统的理论模型,并将其拟合到经验数据中。最佳拟合模型再现了代表性细胞系的预期免疫表型,支持蝙蝠细胞中强大的抗病毒防御能力,这与更高的宿主内病毒传播率估计值相关。总的来说,增强的免疫反应限制了病原体引起的细胞发病,这有助于在宿主内建立快速传播的持续性感染。在与蝙蝠独特的免疫系统不同的二次宿主中出现后,与蝙蝠免疫系统共同进化的快速传播病毒可能会导致毒力增强。