San-Juan-Vergara Homero, Peeples Mark E, Lockey Richard F, Mohapatra Shyam S
The Joy McCann Culverhouse Airways Disease Research Center, Division of Allergy and Immunology, Department of Internal Medicine, College of Medicine, University of South Florida, Tampa, FL 33612, USA.
J Virol. 2004 Dec;78(24):13717-26. doi: 10.1128/JVI.78.24.13717-13726.2004.
Respiratory syncytial virus (RSV) infection activates protein kinase C (PKC), but the precise PKC isoform(s) involved and its role(s) remain to be elucidated. On the basis of the activation kinetics of different signaling pathways and the effect of various PKC inhibitors, it was reasoned that PKC activation is important in the early stages of RSV infection, especially RSV fusion and/or replication. Herein, the role of PKC-alpha during the early stages of RSV infection in normal human bronchial epithelial cells is determined. The results show that the blocking of PKC-alpha activation by classical inhibitors, pseudosubstrate peptides, or the overexpression of dominant-negative mutants of PKC-alpha in these cells leads to significantly decreased RSV infection. RSV induces phosphorylation, activation, and cytoplasm-to-membrane translocation of PKC-alpha. Also, PKC-alpha colocalizes with virus particles and is required for RSV fusion to the cell membrane. Thus, PKC-alpha could provide a new pharmacological target for controlling RSV infection.
呼吸道合胞病毒（RSV）感染可激活蛋白激酶C（PKC），但具体涉及的PKC亚型及其作用仍有待阐明。基于不同信号通路的激活动力学以及各种PKC抑制剂的作用效果，推测PKC激活在RSV感染的早期阶段很重要，尤其是在RSV融合和/或复制过程中。在此，确定了PKC-α在正常人支气管上皮细胞RSV感染早期阶段的作用。结果表明，在这些细胞中，经典抑制剂、假底物肽或PKC-α显性负突变体的过表达阻断PKC-α激活会导致RSV感染显著降低。RSV诱导PKC-α的磷酸化、激活以及从细胞质到细胞膜的转位。此外，PKC-α与病毒颗粒共定位，并且是RSV与细胞膜融合所必需的。因此，PKC-α可为控制RSV感染提供新的药理学靶点。
