Dumitru Claudia Alexandra, Dreschers Stephan, Gulbins Erich
Department of Molecular Biology, University of Duisburg-Essen, Germany.
Cell Physiol Biochem. 2006;17(3-4):159-66. doi: 10.1159/000092077. Epub 2006 Mar 14.
Rhinoviral infections belong to the most frequent human infections characterized by common cold, chronic bronchitis, exacerbations of asthma, otitis media and sinusitis. Here, we define molecular mechanisms that mediate infections of human epithelial cells with human rhinovirus strain 14 (RV14). We demonstrate that RV14 activates p38-MAPKinase (p38-K) in a biphasic time course. Early stimulation of p38-K by RV14 was observed a few minutes after initiation of the infection, while the late increase of p38-K activity occurred 7-12 hrs upon infection. The stimulation of p38-K was mediated by the small G-protein RhoA,which was activated by RV14. Transfection of a genetic construct preventing RhoA activation blocked RV14-induced p38-K activation. Further, integrity of cholesterol and sphingolipid-enriched membrane domains was required for RV14-mediated p38-K activation, which was inhibited by destruction of membrane rafts. The data indicate that RV employs a signaling cascade from membrane rafts via the small G-protein RhoA to p38-K to infect human cells.
鼻病毒感染属于最常见的人类感染，其特征为普通感冒、慢性支气管炎、哮喘加重、中耳炎和鼻窦炎。在此，我们确定了介导人鼻病毒14型（RV14）感染人上皮细胞的分子机制。我们证明，RV14以双相时间进程激活p38丝裂原活化蛋白激酶（p38-K）。在感染开始后几分钟就观察到RV14对p38-K的早期刺激，而p38-K活性的后期增加发生在感染后7-12小时。p38-K的刺激由小G蛋白RhoA介导，RhoA被RV14激活。转染阻止RhoA激活的基因构建体可阻断RV14诱导的p38-K激活。此外，富含胆固醇和鞘脂的膜结构域的完整性是RV14介导的p38-K激活所必需的，膜筏的破坏可抑制这种激活。数据表明，RV利用从膜筏经小G蛋白RhoA到p38-K的信号级联来感染人类细胞。
