Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523-1682, USA.
Cell Host Microbe. 2010 Aug 19;8(2):196-207. doi: 10.1016/j.chom.2010.07.003.
How viral transcripts are protected from the cellular RNA decay machinery and the importance of this protection for the virus are largely unknown. We demonstrate that Sindbis virus, a prototypical single-stranded arthropod-borne alphavirus, uses U-rich 3' UTR sequences in its RNAs to recruit a known regulator of cellular mRNA stability, the HuR protein, during infections of both human and vector mosquito cells. HuR binds viral RNAs with high specificity and affinity. Sindbis virus infection induces the selective movement of HuR out of the mammalian cell nucleus, thereby increasing the available cytoplasmic HuR pool. Finally, knockdown of HuR results in a significant increase in the rate of decay of Sindbis virus RNAs and diminishes viral yields in both human and mosquito cells. These data indicate that Sindbis virus and likely other alphaviruses usurp the HuR protein to avoid the cellular mRNA decay machinery and maintain a highly productive infection.
病毒转录本如何免受细胞 RNA 降解机制的影响，以及这种保护对于病毒的重要性在很大程度上是未知的。我们证明，辛德毕斯病毒（一种典型的单链节肢动物传播的阿尔法病毒）在人类和媒介蚊子细胞的感染过程中，利用其 RNA 中的富含 U 的 3'UTR 序列招募一种已知的细胞 mRNA 稳定性调节剂 HuR 蛋白。HuR 特异性和亲和力高的结合病毒 RNA。辛德毕斯病毒感染诱导 HuR 从哺乳动物细胞核中的选择性运动，从而增加了可用的细胞质 HuR 池。最后，HuR 的敲低导致辛德毕斯病毒 RNA 衰变率显著增加，并减少了人类和蚊子细胞中的病毒产量。这些数据表明，辛德毕斯病毒和可能其他阿尔法病毒利用 HuR 蛋白逃避细胞 mRNA 降解机制并维持高度有效的感染。
