The poliovirus replication machinery can escape inhibition by an antiviral drug that targets a host cell protein
The poliovirus replication machinery can escape inhibition by an antiviral drug that targets a host cell protein
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DOI：
10.1128/jvi.78.7.3378-3386.2004
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发表时间：
2004-04-01
影响因子：
5.4
通讯作者：
Andino, R
中科院分区：
文献类型：
--
作者：
Crotty, S;Saleh, MC;Andino, R
病毒复制依赖于与宿主因子的特定相互作用。例如，脊髓灰质炎病毒RNA复制需要与细胞内膜相结合。布雷菲德菌素A（BFA）能诱导细胞分泌装置发生重大重排，是脊髓灰质炎病毒RNA复制的一种强效抑制剂。关于病毒复制复合物与宿主膜之间关系的大多数方面仍不清楚。为了探究这些相互作用，我们采用了一种遗传学方法，并分离出了抗BFA的脊髓灰质炎病毒变体。病毒蛋白2C和3A内的突变使脊髓灰质炎病毒对BFA产生抗性。在没有BFA的情况下，含有这些突变中的一种或两种的病毒与野生型病毒复制情况相似。在有BFA存在时，在2C或3A上携带单一突变的病毒表现出一种中间生长表型，而双突变体则完全具有抗性。病毒蛋白2C和3A在RNA复制和囊泡形成中都起着关键作用。抗BFA突变体的鉴定可能有助于鉴定诱导囊泡形成和RNA复制所必需的与细胞膜相关的蛋白质。重要的是，我们的数据强调了病毒成功复制所需的宿主 - 病毒相互作用具有显著的可塑性。
Viral replication depends on specific interactions with host factors. For example, poliovirus RNA replication requires association with intracellular membranes. Brefeldin A (BFA), which induces a major rearrangement of the cellular secretory apparatus, is a potent inhibitor of poliovirus RNA replication. Most aspects governing the relationship between viral replication complex and the host membranes remain poorly defined. To explore these interactions, we used a genetic approach and isolated BFA-resistant poliovirus variants. Mutations within viral proteins 2C and 3A render poliovirus resistant to BFA. In the absence of BFA, viruses containing either or both of these mutations replicated similarly to wild type. In the presence of BFA, viruses carrying a single mutation in 2C or 3A exhibited an intermediate-growth phenotype, while the double mutant was fully resistant. The viral proteins 2C and 3A have critical roles in both RNA replication and vesicle formation. The identification of BFA resistant mutants may facilitate the identification of cellular membrane-associated proteins necessary for induction of vesicle formation and RNA replication. Importantly, our data underscore the dramatic plasticity of the host-virus interactions required for successful viral replication.