Caliciviruses differ in their functional requirements for eIF4F components
Caliciviruses differ in their functional requirements for eIF4F components
复制标题
DOI：
10.1074/jbc.m602230200
复制
发表时间：
2006-09-01
影响因子：
4.8
通讯作者：
Goodfellow, Ian G.
中科院分区：
文献类型：
--
作者：
Chaudhry, Yasmin;Nayak, Arabinda;Goodfellow, Ian G.
两类病毒，即马铃薯Y病毒科和杯状病毒科的成员，使用一种新的机制来启动蛋白质合成，该机制涉及翻译起始因子与共价连接到病毒RNA的病毒蛋白（称为VPg）的相互作用。杯状病毒VPg蛋白可与起始因子eIF 4 E和eIF 3直接相互作用。猫杯状病毒（FCV）RNA的翻译起始需要eIF 4 E，因为它被重组4 E-BP 1抑制。然而，到目前为止，还没有进行关于诺如病毒翻译起始的功能研究，因为缺乏合适的VPg连接的病毒RNA来源。我们现在已经使用最近鉴定的鼠诺如病毒（MNV）作为诺如病毒翻译的模型系统，并扩展了我们以前的研究与FCV RNA检查其他eIF 4F组件在翻译起始中的作用。我们现在证明，与FCV一样，MNV VPg直接与eIF 4 E相互作用，尽管与FCV RNA不同，MNV RNA的翻译对4 E-BP 1、eIF 4 E耗尽或口蹄疫病毒Lb蛋白酶介导的eIF 4G裂解不敏感。我们还表明，FCV和MNV RNA翻译需要eIF 4F复合物的RNA解旋酶组分，即eIF 4A，因为翻译是敏感的（尽管程度不同）显性阴性形式和eIF 4A（马尿酸）的小分子抑制剂。这些结果表明，杯状病毒RNA不同的eIF 4F翻译起始复合物的组分方面的要求。
Two classes of viruses, namely members of the Potyviridae and Caliciviridae, use a novel mechanism for the initiation of protein synthesis that involves the interaction of translation initiation factors with a viral protein covalently linked to the viral RNA, known as VPg. The calicivirus VPg proteins can interact directly with the initiation factors eIF4E and eIF3. Translation initiation on feline calicivirus (FCV) RNA requires eIF4E because it is inhibited by recombinant 4E-BP1. However, to date, there have been no functional studies carried out with respect to norovirus translation initiation, because of a lack of a suitable source of VPg-linked viral RNA. We have now used the recently identified murine norovirus (MNV) as a model system for norovirus translation and have extended our previous studies with FCV RNA to examine the role of the other eIF4F components in translation initiation. We now demonstrate that, as with FCV, MNV VPg interacts directly with eIF4E, although, unlike FCV RNA, translation of MNV RNA is not sensitive to 4E-BP1, eIF4E depletion, or foot-and-mouth disease virus Lb protease-mediated cleavage of eIF4G. We also demonstrate that both FCV and MNV RNA translation require the RNA helicase component of the eIF4F complex, namely eIF4A, because translation was sensitive (albeit to different degrees) to a dominant negative form and to a small molecule inhibitor of eIF4A (hippuristanol). These results suggest that calicivirus RNAs differ with respect to their requirements for the components of the eIF4F translation initiation complex.