Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
Autophagy. 2013 May;9(5):797-8. doi: 10.4161/auto.23959. Epub 2013 Feb 26.
Autophagy is a cellular response activated by many pathogens, but the mechanism of activation is largely unknown. Recently we showed for the first time that rotavirus initiates the autophagy pathway through a calcium-mediated mechanism. Expression of the rotavirus-encoded NSP4, a pore-forming protein (viroporin), elicits the release of endoplasmic reticulum (ER) lumenal calcium into the cytoplasm of the infected cell. The increased cytoplasmic calcium activates a calcium signaling pathway involving calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) and 5' adenosine monophosphate-activated protein kinase (AMPK) to trigger autophagy. Rotavirus further manipulates autophagy membrane trafficking to transport viral ER-associated proteins to viroplasms, sites of viral genome replication and immature particle assembly. Transport of viral proteins to viroplasms is required for assembly of infectious virus. Thus, NSP4, a multifunctional viral protein known to regulate infectious particle assembly, also modulates membrane trafficking by orchestrating the activation of autophagy to benefit viral replication.
自噬是一种被许多病原体激活的细胞反应，但激活的机制在很大程度上尚不清楚。最近，我们首次表明轮状病毒通过钙介导的机制启动自噬途径。轮状病毒编码的 NSP4（一种形成孔的蛋白（病毒孔蛋白））的表达引发内质网（ER）腔钙释放到感染细胞的细胞质中。细胞质中增加的钙激活了涉及钙/钙调蛋白依赖性蛋白激酶激酶 2（CAMKK2）和 5' 腺苷单磷酸激活蛋白激酶（AMPK）的钙信号通路，从而引发自噬。轮状病毒进一步操纵自噬膜运输，将病毒 ER 相关蛋白运输到病毒包涵体，病毒基因组复制和不成熟颗粒组装的部位。病毒蛋白向病毒包涵体的运输是组装感染性病毒所必需的。因此，NSP4 是一种已知调节感染性颗粒组装的多功能病毒蛋白，它还通过协调自噬的激活来促进病毒复制，从而调节膜运输。
