A five-amino-acid deletion of the eastern equine encephalitis virus capsid protein attenuates replication in mammalian systems but not in mosquito cells
A five-amino-acid deletion of the eastern equine encephalitis virus capsid protein attenuates replication in mammalian systems but not in mosquito cells
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DOI：
10.1128/jvi.01283-07
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发表时间：
2008-07-01
影响因子：
5.4
通讯作者：
Basler, Christopher F.
中科院分区：
文献类型：
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作者：
Aguilar, Patricia V.;Leung, Lawrence W.;Basler, Christopher F.
东方马脑炎病毒（EEEV）是一种人类和兽医病原体，引起散发的致命神经系统疾病病例。我们之前已经证明EEEV的衣壳蛋白是宿主细胞基因表达的有效抑制剂，并且这种功能映射到蛋白质的氨基端。我们现在确定衣壳N端内的氨基酸55至75对抑制宿主细胞基因表达至关重要。对表达突变衣壳蛋白的稳定EEEV复制子的分析证实了这些定位数据。当将衣壳区域内的5到20个氨基酸缺失引入感染性EEEV时，突变体在Vero细胞中表现出延迟复制。然而，5-氨基酸缺失突变体在C710蚊子细胞中的复制并未受到影响，这表明病毒的复制和组装受到细胞特异性影响。5-和20-氨基酸缺失突变病毒在细胞培养中表现出对干扰素（IFN）的敏感性增加，在小鼠中表现出复制受损和完全衰减。总之，我们已经确定了EEEV衣壳蛋白内的一个区域，该区域有助于抑制宿主基因表达并保护EEEV免受ifn的抗病毒作用。该区域也是EEEV发病机制的关键区域。
Eastern equine encephalitis virus (EEEV) is a human and veterinary pathogen that causes sporadic cases of fatal neurological disease. We previously demonstrated that the capsid protein of EEEV is a potent inhibitor of host cell gene expression and that this function maps to the amino terminus of the protein. We now identify amino acids 55 to 75, within the N terminus of the capsid, as critical for the inhibition of host cell gene expression. An analysis of stable EEEV replicons expressing mutant capsid proteins corroborated these mapping data. When deletions of 5 to 20 amino acids within this region of the capsid were introduced into infectious EEEV, the mutants exhibited delayed replication in Vero cells. However, the replication of the 5-amino-acid deletion mutant in C710 mosquito cells was not affected, suggesting that virus replication and assembly were affected in a cell-specific manner. Both 5- and 20-amino-acid deletion mutant viruses exhibited increased sensitivity to interferon (IFN) in cell culture and impaired replication and complete attenuation in mice. In summary, we have identified a region within the capsid protein of EEEV that contributes to the inhibition of host gene expression and to the protection of EEEV from the antiviral effects of IFNs. This region is also critical for EEEV pathogenesis.