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Functions of the Respiratory Syncytial Virus SH and P Proteins

出版	Pennsylvania State University, 2010
URL	http://books.google.com.hk/books?id=qmGQAQAACAAJ&hl=&source=gbs_api

註釋The RSV SH is an accessory protein involved in RSV pathogenesis but not necessary for virus growth. In contrast, the RSV phosphoprotein (P) is necessary for viral RNA synthesis and a P deletion mutant is not viable. The P protein is an integral part of the polymerase complex involved in transcription and replication and it is the major phosphorylated species of the virus. The role of P protein phosphorylation for the proteins function is not completely understood. Recent studies in our lab suggest that the cellular kinase Akt is important for the RNA synthesis of non-segmented negative-sense RNA viruses. To study the role of Akt in RSV RNA synthesis, Akt activity was inhibited with small molecule inhibitors, siRNA and dominant negative constructs. Inhibition of Akt reduced RSV RNA synthesis, protein production and RSV titers. In addition, a small molecule inhibitor of Akt activation also reduced P protein phosphorylation, suggesting that P is a target of Akt. Serine 86 of P was identified as the Akt phosphorylation site in vitro. Mutation of that serine to an alanine significantly reduced P protein phosphorylation by Akt in an in vitro kinase assay. Phosphorylation at serine 86 was also detected in P protein from RSV infected cells. These results suggest that Akt inhibitors could be developed for RSV therapeutics. Identification of the site of Akt phosphorylation in P during RSV infection could lead to a new strategy in the development of an RSV vaccine.