Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence
Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence
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DOI：
10.7554/elife.48401
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发表时间：
2020-02-03
期刊：
影响因子：
7.7
通讯作者：
van Leeuwen, Anieke
中科院分区：
文献类型：
--
作者：
Brook, Cara E.;Boots, Mike;van Leeuwen, Anieke
蝙蝠携带剧毒的人畜共患病毒而不患病。为了阐明人畜共患病的出现，需要对蝙蝠的病毒承载能力（包括独特的构成性免疫途径）对细胞尺度病毒动力学的影响有一个机制上的了解。我们对表达诱导型和组成型免疫表型的蝙蝠细胞系进行了病毒感染性实验，然后建立了我们体外系统的理论模型，并与经验数据进行了拟合。最佳拟合模型概括了代表性细胞系的预期免疫表型，支持蝙蝠细胞中与宿主内病毒传播率较高的估计相关的强大抗病毒防御。一般来说，增强的免疫反应限制了病原体诱导的细胞发病率，这有助于在宿主内建立快速传播的持续感染。随着蝙蝠免疫系统进化而来的快速传播病毒，在进入具有与蝙蝠特有免疫系统不同的免疫系统的第二宿主后，可能会导致毒性增强。
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 in vitro 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.