Naghavi Mojgan H, Valente Susana, Hatziioannou Theodora, de Los Santos Kenia, Wen Ying, Mott Christina, Gundersen Gregg G, Goff Stephen P
Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
EMBO J. 2007 Jan 10;26(1):41-52. doi: 10.1038/sj.emboj.7601475. Epub 2006 Dec 14.
In a functional screen of mammalian complementary DNA libraries, we identified moesin as a novel gene whose overexpression blocks infection by murine leukemia viruses and human immunodeficiency virus type 1 in human and rodent lines, before the initiation of reverse transcription. Knockdown of moesin by RNA interference resulted in enhanced infection, suggesting that even the endogenous basal levels of moesin in rat fibroblasts are sufficient to limit virus infection. Moesin acts as a crosslinker between plasma membrane and actin filaments, as well as a signal transducer in responses involving cytoskeletal remodeling. Moesin overexpression was found to downregulate the formation of stable microtubules, whereas knockdown of moesin increased stable microtubule formation. A virus-resistant mutant cell line also displayed decreased stable microtubule levels, and virus-sensitive revertants recovered from the mutant line showed restoration of the stable microtubules, suggesting that these cytoskeletal networks play an important role in early post-entry events in the retroviral lifecycle. Together, these results suggest that moesin negatively regulates stable microtubule networks and is a natural determinant of cellular sensitivity to retroviral infection.
在对哺乳动物互补DNA文库进行的功能筛选中，我们鉴定出埃兹蛋白（moesin）是一个新基因，其过表达在逆转录开始之前，可阻断小鼠白血病病毒和1型人类免疫缺陷病毒在人和啮齿类细胞系中的感染。通过RNA干扰敲低埃兹蛋白导致感染增强，这表明即使是大鼠成纤维细胞中埃兹蛋白的内源性基础水平也足以限制病毒感染。埃兹蛋白作为质膜与肌动蛋白丝之间的交联蛋白，以及涉及细胞骨架重塑反应中的信号转导分子发挥作用。研究发现，埃兹蛋白过表达会下调稳定微管的形成，而敲低埃兹蛋白则会增加稳定微管的形成。一个抗病毒突变细胞系也表现出稳定微管水平降低，从该突变系中恢复的病毒敏感回复株显示稳定微管得以恢复，这表明这些细胞骨架网络在逆转录病毒生命周期的早期进入后事件中起重要作用。总之，这些结果表明埃兹蛋白对稳定微管网络起负调控作用，并且是细胞对逆转录病毒感染敏感性的天然决定因素。
