Asenjo Ana, González-Armas Juan C, Villanueva Nieves
Centro Nacional de Microbiología, Instituto de Salud Carlos III, Ctra, Majadahonda, Madrid, Spain.
Virology. 2008 Oct 10;380(1):26-33. doi: 10.1016/j.virol.2008.06.045. Epub 2008 Aug 15.
The human respiratory syncytial virus (HRSV) structural P protein, phosphorylated at serine (S) and threonine (T) residues, is a co-factor of viral RNA polymerase. The phosphorylation of S54 is controlled by the coordinated action of two cellular enzymes: a lithium-sensitive kinase, probably glycogen synthetase kinase (GSK-3) beta and protein phosphatase 2A (PP2A). Inhibition of lithium-sensitive kinase, soon after infection, blocks the viral growth cycle by inhibiting synthesis and/or accumulation of viral RNAs, proteins and extracellular particles. P protein phosphorylation at S54 is required to liberate viral ribonucleoproteins (RNPs) from M protein, during the uncoating process. Kinase inhibition, late in infection, produces a decrease in genomic RNA and infectious viral particles. LiCl, intranasally applied to mice infected with HRSV A2 strain, reduces the number of mice with virus in their lungs and the virus titre. Administration of LiCl to humans via aerosol should prevent HRSV infection, without secondary effects.
人呼吸道合胞病毒（HRSV）的结构P蛋白在丝氨酸（S）和苏氨酸（T）残基处发生磷酸化，是病毒RNA聚合酶的辅助因子。S54的磷酸化受两种细胞酶的协同作用控制：一种锂敏感激酶，可能是糖原合成酶激酶（GSK-3）β和蛋白磷酸酶2A（PP2A）。感染后不久抑制锂敏感激酶，通过抑制病毒RNA、蛋白质和细胞外颗粒的合成和/或积累来阻断病毒生长周期。在脱壳过程中，S54处的P蛋白磷酸化是从M蛋白中释放病毒核糖核蛋白（RNP）所必需的。感染后期的激酶抑制会导致基因组RNA和感染性病毒颗粒减少。将LiCl经鼻内应用于感染HRSV A2株的小鼠，可减少肺部有病毒的小鼠数量和病毒滴度。通过气雾剂向人类施用LiCl应可预防HRSV感染，且无副作用。
