CRM1-dependent nuclear export of dengue virus type 2 NS5.
CRM1-dependent nuclear export of dengue virus type 2 NS5.
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DOI：
10.1002/0470058005.ch11
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发表时间：
2006-01-01
影响因子：
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通讯作者：
Jans, David A
中科院分区：
文献类型：
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作者：
Pryor, Melinda J;Rawlinson, Stephen M;Jans, David A
登革病毒多结构域RNA聚合酶NS5已在哺乳动物感染细胞系统的细胞核中被观察到。我们之前的研究表明，NS5核定位是由NS5域间区域的两个核靶向信号介导的，这些信号被细胞内转运蛋白输入超家族的不同成员识别。有趣的是，我们最近发现，在转染表达NS5的Vero细胞和登革热病毒2型感染的Vero细胞中，基于使用CRM1特异性抑制剂leptomycin B (LMB)， NS5也具有由输入蛋白家族成员CRM1（输出蛋白1）从细胞核输出的能力。LMB处理Vero细胞导致两个系统的核积累增加，有趣的是，后者导致病毒产生动力学的改变。我们的研究结果表明，在感染周期的特定时间，NS5的亚细胞转运可能是病毒产生动力学的核心；扰乱这种贩运可能是开发新的抗病毒治疗方法的可行方法。
The dengue virus multidomain RNA polymerase NS5 has been observed in the nucleus in mammalian infected cell systems. We previously showed that NS5 nuclear localization is mediated by two nuclear targeting signals within the NS5 interdomain region that are recognized by distinct members of the importin superfamily of intracellular transporters. Intriguingly, we have recently found that NS5 also possesses the ability to be exported from the nucleus by the importin family member CRM1 (exportin 1) both in Vero cells transfected to express NS5, and in dengue virus type 2 infected Vero cells, based on use of the CRM1-specific inhibitor leptomycin B (LMB). LMB treatment of Vero cells resulted in increased nuclear accumulation in both systems, and interestingly in the latter, resulted in an alteration in the kinetics of virus production. Our results imply that subcellular trafficking of NS5 at particular times in the infectious cycle may be central to the kinetics of virus production; perturbing this trafficking may represent a viable approach to develop new antiviral therapeutics.