Adaptation to host cell environment during experimental evolution of Zika virus.
Adaptation to host cell environment during experimental evolution of Zika virus.
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DOI：
10.1038/s42003-022-03902-y
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发表时间：
2022-10-21
影响因子：
5.9
通讯作者：
中科院分区：
文献类型：
--
作者：
寨卡病毒（ZIKV）感染可导致人类严重的发育和神经缺陷。 I/III 型干扰素反应控制 ZIKV 感染和病理过程，但该病毒已进化出各种机制来击败这些宿主反应。在这里，我们建立了一个管道，以高分辨率描绘受控宿主细胞环境中 ZIKV 的遗传进化。我们发现，连续传代的 ZIKV 获得了增强的感染性，同时对 TLR3 诱导的限制产生了抗性。我们建立了一个数学模型，表明传染性增加是由于感染和病毒复制之间的时间延迟缩短所致。我们发现这种适应是细胞类型特异性的，这表明不同的细胞环境可能驱动病毒沿着不同的途径进化。 ZIKV 群体的深度测序精确定位了突变，其频率的增加在时间上与适应表型的获得一致。我们对 S455L 进行功能验证，它是 ZIKV 包膜 (E) 蛋白的替代物，概括了适应的表型。它在 E 结构上的定位表明其在蛋白质重折叠/稳定性方面具有假定的功能。总而言之，我们的结果揭示了 ZIKV 对细胞环境的适应，导致复制开始加速，并对 TLR3 诱导的抗病毒反应产生抵抗。我们的工作提供了关于寨卡病毒对宿主细胞的适应和免疫逃逸机制的见解。体外分析和计算模型表明，寨卡病毒会随着时间的推移适应宿主的细胞环境
Zika virus (ZIKV) infection can cause important developmental and neurological defects in Humans. Type I/III interferon responses control ZIKV infection and pathological processes, yet the virus has evolved various mechanisms to defeat these host responses. Here, we established a pipeline to delineate at high-resolution the genetic evolution of ZIKV in a controlled host cell environment. We uncovered that serially passaged ZIKV acquired increased infectivity and simultaneously developed a resistance to TLR3-induced restriction. We built a mathematical model that suggests that the increased infectivity is due to a reduced time-lag between infection and viral replication. We found that this adaptation is cell-type specific, suggesting that different cell environments may drive viral evolution along different routes. Deep-sequencing of ZIKV populations pinpointed mutations whose increased frequencies temporally coincide with the acquisition of the adapted phenotype. We functionally validated S455L, a substitution in ZIKV envelope (E) protein, recapitulating the adapted phenotype. Its positioning on the E structure suggests a putative function in protein refolding/stability. Taken together, our results uncovered ZIKV adaptations to the cellular environment leading to accelerated replication onset coupled with resistance to TLR3-induced antiviral response. Our work provides insights into Zika virus adaptation to host cells and immune escape mechanisms. In vitro analyses and computational modelling indicate that Zika virus adapts to the cellular environment of its host over time
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影响因子：
30.3
作者：
Assil, Sonia;Coleon, Severin;Dreux, Marlene
通讯作者：
Dreux, Marlene
影响因子：
64.8
作者：
Alexopoulou, L;Holt, AC;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
3.4
作者：
Acosta, Eliana G.;Castilla, Viviana;Damonte, Elsa B.
通讯作者：
Damonte, Elsa B.
影响因子：
8
作者：
Jurado, Kellie Ann;Simoni, Michael K.;Fikrig, Erol
通讯作者：
Fikrig, Erol
DOI：
10.1073/pnas.1807690115
发表时间：
2018-09-25
影响因子：
11.1
作者：
Carlin AF;Vizcarra EA;Branche E;Viramontes KM;Suarez-Amaran L;Ley K;Heinz S;Benner C;Shresta S;Glass CK
通讯作者：
Glass CK