The YLDL sequence within Sendai virus m protein is critical for budding of virus-like particles and interacts with Alix/AIP1 independently of C protein
The YLDL sequence within Sendai virus m protein is critical for budding of virus-like particles and interacts with Alix/AIP1 independently of C protein
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DOI：
10.1128/jvi.02218-06
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发表时间：
2007-03-01
影响因子：
5.4
通讯作者：
Sakaguchi, Takemasa
中科院分区：
文献类型：
--
作者：
Irie, Takashi;Shimazu, Yukie;Sakaguchi, Takemasa
对于许多包膜病毒，已报道细胞多囊体（MVB）分选机制用于有效的病毒出芽。基质和Gag蛋白已显示含有一个或两个L结构域基序（PPxY、PT/SAP、YPDL和FPIV），其中一些与参与MVB分选的宿主细胞蛋白特异性相互作用，所述宿主细胞蛋白被募集到病毒出芽位点。然而，对于许多包膜病毒，L-结构域基序尚未被确定，MVB分选机制在病毒出芽中的参与仍然是未知的。仙台病毒（SeV）基质蛋白M和辅助蛋白C均通过与阿利克斯/AIP 1的物理相互作用而促进病毒出芽。M蛋白中的YLDL序列具有L结构域活性，其与阿利克斯/AIP 1（1-211）N端的特异性相互作用对于M蛋白的病毒样颗粒（VLP）出芽非常重要。此外，M-VLP出芽被某些缺失突变形式的阿利克斯/AIP 1的过表达和内源性阿利克斯/AIP 1与特异性小干扰RNA的耗竭所抑制。YLDL序列不能被其他L结构域基序取代，如PPxY和PT/SAP，甚至YPxL。C蛋白也能够与阿利克斯/AIP 1（212-357）的N末端物理相互作用，并独立于M-阿利克斯/AIP 1相互作用而增强M-VLP出芽，尽管它不从转染的细胞本身释放。我们的研究结果表明，多种病毒蛋白与阿利克斯/AIP 1的相互作用可以提高利用细胞MVB分选机制进行有效SeV出芽的效率。
For many enveloped viruses, cellular multivesicullar body (MVB) sorting machinery has been reported to be utilized for efficient viral budding. Matrix and Gag proteins have been shown to contain one or two L-domain motifs (PPxY, PT/SAP, YPDL, and FPIV), some of which interact specifically with host cellular proteins involved in MVB sorting, which are recruited to the viral budding site. However, for many enveloped viruses, L-domain motifs have not yet been identified and the involvement of MVB sorting machinery in viral budding is still unknown. Here we show that both Sendai virus (SeV) matrix protein M and accessory protein C contribute to virus budding by physically interacting with Alix/AIP1 A YLDL sequence within the M protein showed L-domain activity, and its specific interaction with the N terminus of Alix/AIP1(1-211) was important for the budding of virus-like particles (VLPs) of M protein. In addition, M-VLP budding was inhibited by the overexpression of some deletion mutant forms of Alix/AIP1 and depletion of endogenous Alix/AIP1 with specific small interfering RNAs. The YLDL sequence was not replaceable by other L-domain motifs, such as PPxY and PT/SAP, and even YPxL. C protein was also able to physically interact with the N terminus of Alix/AIP1(212-357) and enhanced M-VLP budding independently of M-Alix/AIP1 interaction, although it was not released from the transfected cells itself. Our results suggest that the interaction of multiple viral proteins with Alix/AIP1 may enhance the efficiency of the utilization of cellular MVB sorting machinery for efficient SeV budding.