Suppression of astrovirus replication by an ERK1/2 inhibitor
Suppression of astrovirus replication by an ERK1/2 inhibitor
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DOI：
10.1128/jvi.02193-07
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发表时间：
2008-08-01
影响因子：
5.4
通讯作者：
Schultz-Cherry, Stacey
中科院分区：
文献类型：
--
作者：
Moser, Lindsey A.;Schultz-Cherry, Stacey
人星状病毒是与自限性腹泻相关的无包膜、正义单链RNA病毒。虽然它们被认为是幼儿疾病的主要原因，但参与星状病毒复制的细胞因子尚未明确。细胞外信号调节激酶（ERK）通路已被证明可以调节许多病毒感染，但其在星状病毒感染中的作用尚不清楚。在这份报告中，我们表明，星状病毒激活ERK 1/2在感染早期独立的复制。用特异性ERK抑制剂U 0126抑制ERK活化可显著降低病毒产生。对ERK 1/2调节机制的研究表明，在U 0126处理单层细胞期间，病毒生命周期的所有步骤，包括早期和晚期蛋白表达以及亚基因组和基因组RNA转录都减少了。这些数据支持ERK 1/2在postattachment步骤中的作用，尽管确切的机制仍在调查中。
Human astroviruses are nonenveloped, positive-sense single-strand RNA viruses associated with self-limiting diarrhea. Although they are recognized as a leading cause of disease in young children, the cellular factors involved in astrovirus replication are not well defined. The extracellular signal-regulated kinase (ERK) pathway has been shown to regulate many viral infections, but its role during astrovirus infection is unknown. In this report, we show that astrovirus activates ERK1/2 early in infection independently of replication. Inhibition of ERK activation with U0126, a specific ERK inhibitor, significantly reduced viral production. Investigations into the mechanism of ERK1/2 regulation revealed that all steps of the viral life cycle, including early and late protein expression as well as subgenomic and genomic RNA transcription, were diminished during U0126 treatment of monolayers. These data support a role for ERK1/2 in a postattachment step, although the precise mechanism remains under investigation.