Interferon regulatory factor 3 is a cellular partner of rotavirus NSP1
Interferon regulatory factor 3 is a cellular partner of rotavirus NSP1
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DOI：
10.1128/jvi.76.18.9545-9550.2002
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发表时间：
2002-09-01
影响因子：
5.4
通讯作者：
Hardy, ME
中科院分区：
文献类型：
--
作者：
Graff, JW;Mitzel, DN;Hardy, ME
轮状病毒非结构蛋白NSP 1是轮状病毒基因组中保守性最低的蛋白质，其在复制周期中的功能尚不清楚。我们在酵母双杂交相互作用陷阱中采用NSP 1作为诱饵，以鉴定NSP 1的候选细胞伴侣，这可能为其功能提供线索。干扰素调节因子3（IRF-3）被鉴定为NSP 1相互作用因子。NSP 1在轮状病毒感染的细胞中合成，在谷胱甘肽S-转移酶下拉试验中结合IRF-3，表明这种相互作用不是双杂交系统所独有的。小鼠轮状病毒EW株的NSP 1也与IRF-3相互作用。构建了NSP 1缺失和点突变体以映射NSP 1和IRF-3之间相互作用的重要结构域。这些数据表明，结合结构域驻留在C端的NSP 1和N-末端保守的锌指是重要的，但不足以介导结合IRF-3。我们预测NSP 1在轮状病毒感染的细胞中的作用是抑制IRF-3的激活并减少细胞干扰素应答。
The rotavirus nonstructural protein NSP1 is the least conserved protein in the rotavirus genome, and its function in the replication cycle is not known. We employed NSP1 as bait in the yeast two-hybrid interaction trap to identify candidate cellular partners of NSP1 that may provide clues to its function. Interferon regulatory factor 3 (IRF-3) was identified as an NSP1 interactor. NSP1 synthesized in rotavirus-infected cells bound IRF-3 in a glutathione S-transferase pull-down assay, indicating that the interaction was not unique to the two-hybrid system. NSP1 of murine rotavirus strain EW also interacted with IRF-3. NSP1 deletion and point mutants were constructed to map domains important in the interaction between NSP1 and IRF-3. The data suggest that a binding domain resides in the C terminus of NSP1 and that the N-terminal conserved zinc finger is important but not sufficient to mediate binding to IRF-3. We predict that a role for NSP1 in rotavirus-infected cells is to inhibit activation of IRF-3 and diminish the cellular interferon response.