Enterovirus D68 capsid formation and stability requires acidic compartments.
Enterovirus D68 capsid formation and stability requires acidic compartments.
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肠道病毒 D68 衣壳的形成和稳定性需要酸性隔室。
DOI：
10.1101/2023.06.12.544695
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Jackson,WilliamT
中科院分区：
文献类型：
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作者：
Galitska,Ganna;Jassey,Alagie;Wagner,MichaelA;Pollack,Noah;Jackson,WilliamT
肠道病毒D 68（EV-D 68）是一种传统上与呼吸道感染有关的小核糖核酸病毒，最近被认为与一种称为急性弛缓性肌麻痹的脊髓灰质炎样麻痹症有关。EV-D 68尚未得到充分研究，该领域对该病毒的大部分了解都是基于对脊髓灰质炎病毒的研究。对于脊髓灰质炎病毒，我们以前表明，低pH值促进病毒衣壳成熟，但在这里，我们表明，对于EV-D 68，在特定的感染窗口期间抑制隔室酸化导致衣壳形成和维持缺陷。这些表型伴随着感染细胞的根本变化，病毒复制细胞器聚集在一个紧密的核群中。细胞器酸化在3至4 hpi的狭窄窗口期间是至关重要的，我们称之为“过渡点”，将翻译和峰值RNA复制与衣壳形成、成熟和排出分开。我们的研究结果强调，只有当囊泡从RNA工厂转化为病毒粒子坩埚时，酸化才至关重要。重要信息呼吸道小核糖核酸病毒肠道病毒D 68是急性驰缓性脊髓炎的病原体，急性驰缓性脊髓炎是过去十年发现的一种儿童瘫痪疾病。脊髓灰质炎病毒是另一种与麻痹性疾病相关的小核糖核酸病毒，是一种粪-口病毒，在宿主之间传播时能在酸性环境中存活。在这里，我们跟进我们以前的工作，表明脊髓灰质炎病毒颗粒的成熟裂解需要酸性细胞内隔室。肠道病毒D 68需要酸性囊泡用于病毒颗粒本身的早期步骤、组装和维持。这些数据对于使用酸化阻断治疗来对抗肠道病毒疾病具有强烈的意义。
Enterovirus D68 (EV-D68), a picornavirus traditionally associated with respiratory infections, has recently been linked to a polio-like paralytic condition known as acute flaccid myelitis. EV-D68 is understudied, and much of the field’s understanding of this virus is based on studies of poliovirus. For poliovirus, we previously showed that low pH promotes virus capsid maturation, but here we show that, for EV-D68, inhibition of compartment acidification during a specific window of infection causes a defect in capsid formation and maintenance. These phenotypes are accompanied by radical changes in the infected cell, with viral replication organelles clustering in a tight juxtanuclear grouping. Organelle acidification is critical during a narrow window from 3 to 4 hpi, which we have termed the “transition point,” separating translation and peak RNA replication from capsid formation, maturation, and egress. Our findings highlight that acidification is crucial only when vesicles convert from RNA factories to virion crucibles.IMPORTANCEThe respiratory picornavirus enterovirus D68 is a causative agent of acute flaccid myelitis, a childhood paralysis disease identified in the last decade. Poliovirus, another picornavirus associated with paralytic disease, is a fecal-oral virus that survives acidic environments when passing from host to host. Here, we follow up on our previous work showing a requirement for acidic intracellular compartments for maturation cleavage of poliovirus particles. Enterovirus D68 requires acidic vesicles for an earlier step, assembly, and maintenance of viral particles themselves. These data have strong implications for the use of acidification blocking treatments to combat enterovirus diseases.