Dual function of the nuclear export signal of the Borna disease virus nucleoprotein in nuclear export activity and binding to viral phosphoprotein.
Dual function of the nuclear export signal of the Borna disease virus nucleoprotein in nuclear export activity and binding to viral phosphoprotein.
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DOI：
10.1186/s12985-017-0793-6
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发表时间：
2017-07-11
期刊：
影响因子：
4.8
通讯作者：
Tomonaga K
中科院分区：
文献类型：
--
作者：
Yanai M;Sakai M;Makino A;Tomonaga K
博尔纳病病毒（BoDV）具有负义单链RNA基因组，在细胞核中引起持续感染。由128和131位亮氨酸和133和136位异亮氨酸组成的病毒核蛋白（N）的核输出信号（内斯）与病毒磷蛋白（P）的两个预测结合位点之一重叠。先前的研究表明，高表达的BoDV-P抑制核输出的N;然而，N内斯在与P的相互作用的功能还不清楚。我们研究了亚细胞定位，病毒聚合酶活性，和P-结合能力的BoDV-N内斯突变体。我们还鉴定了含有N.内斯突变的重组BoDV（rBoDV）。在内斯的亮氨酸和异亮氨酸残基中具有四个丙氨酸取代的BoDV-N损害了其细胞质定位，并且消除了聚合酶活性和P结合能力。虽然在位置131处的丙氨酸取代显著增强病毒聚合酶活性，如通过微型基因组测定所确定的，但是携带该突变的rBoDV显示相对于野生型rBoDV的病毒RNA和蛋白质的表达。我们的结果表明BoDV-N内斯在BoDV复制中具有双重功能，即，N的核输出和与P的相互作用，影响核中的病毒聚合酶活性。
Borna disease virus (BoDV), which has a negative-sense, single-stranded RNA genome, causes persistent infection in the cell nucleus. The nuclear export signal (NES) of the viral nucleoprotein (N) consisting of leucine at positions 128 and 131 and isoleucine at positions 133 and 136 overlaps with one of two predicted binding sites for the viral phosphoprotein (P). A previous study demonstrated that higher expression of BoDV-P inhibits nuclear export of N; however, the function of N NES in the interaction with P remains unclear. We examined the subcellular localization, viral polymerase activity, and P-binding ability of BoDV-N NES mutants. We also characterized a recombinant BoDV (rBoDV) harboring an NES mutation of N. BoDV-N with four alanine-substitutions in the leucine and isoleucine residues of the NES impaired its cytoplasmic localization and abolished polymerase activity and P-binding ability. Although an alanine-substitution at position 131 markedly enhanced viral polymerase activity as determined by a minigenome assay, rBoDV harboring this mutation showed expression of viral RNAs and proteins relative to that of wild-type rBoDV. Our results demonstrate that BoDV-N NES has a dual function in BoDV replication, i.e., nuclear export of N and an interaction with P, affecting viral polymerase activity in the nucleus.
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影响因子：
14.8
作者：
Kelley LA;Mezulis S;Yates CM;Wass MN;Sternberg MJ
通讯作者：
Sternberg MJ
影响因子：
5.4
作者：
Chase, Geoffrey;Mayer, Daniel;Schwemmle, Martin
通讯作者：
Schwemmle, Martin
DOI：
10.1073/pnas.0808101106
发表时间：
2009-03-10
影响因子：
11.1
作者：
Neumann, Piotr;Lieber, Diana;Stubbs, Milton T.
通讯作者：
Stubbs, Milton T.
DOI：
10.1073/pnas.89.23.11486
发表时间：
1992-12-01
影响因子：
11.1
作者：
BRIESE, T;DELATORRE, JC;LIPKIN, WI
通讯作者：
LIPKIN, WI
影响因子：
4.8
作者：
Schneider, U;Blechschmidt, K;Staeheli, P
通讯作者：
Staeheli, P