Gabriel Gülsah, Herwig Astrid, Klenk Hans-Dieter
Institute of Virology, Philipps University Marburg, Germany.
PLoS Pathog. 2008 Feb 8;4(2):e11. doi: 10.1371/journal.ppat.0040011.
We have previously reported that mutations in the polymerase proteins PB1, PB2, PA, and the nucleocapsid protein NP resulting in enhanced transcription and replication activities in mammalian cells are responsible for the conversion of the avian influenza virus SC35 (H7N7) into the mouse-adapted variant SC35M. We show now that adaptive mutations D701N in PB2 and N319K in NP enhance binding of these proteins to importin alpha1 in mammalian cells. Enhanced binding was paralleled by transient nuclear accumulation and cytoplasmic depletion of importin alpha1 as well as increased transport of PB2 and NP into the nucleus of mammalian cells. In avian cells, enhancement of importin alpha1 binding and increased nuclear transport were not observed. These findings demonstrate that adaptation of the viral polymerase to the nuclear import machinery plays an important role in interspecies transmission of influenza virus.
我们之前报道过，聚合酶蛋白PB1、PB2、PA以及核衣壳蛋白NP中的突变导致在哺乳动物细胞中转录和复制活性增强，这些突变是禽流感病毒SC35（H7N7）转变为适应小鼠的变体SC35M的原因。我们现在表明，PB2中的适应性突变D701N和NP中的N319K增强了这些蛋白与哺乳动物细胞中输入蛋白α1的结合。结合增强伴随着输入蛋白α1的短暂核内积累和胞质耗竭，以及PB2和NP向哺乳动物细胞核内转运的增加。在禽类细胞中，未观察到输入蛋白α1结合增强和核转运增加。这些发现表明，病毒聚合酶对核输入机制的适应在流感病毒的种间传播中起重要作用。
