Mizutani T
Department of Virology 1, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama, Tokyo, Japan.
Ann N Y Acad Sci. 2007 Apr;1102(1):86-95. doi: 10.1196/annals.1408.006.
Severe acute respiratory syndrome (SARS) is a newly found infectious disease that is caused by a novel human coronavirus, SARS coronavirus (SARS-CoV). Because the mortality rate of SARS patients is very high, understanding the pathological mechanisms of SARS not only in vivo but in vitro is important for the prevention of SARS. Activation of signaling pathways caused by SARS-CoV infection leads to the phosphorylation and activation of downstream molecules. Two conflicting cellular programs, apoptosis to eliminate virus-infected cells and survival to delay apoptosis by producing antiviral cytokines, occur in SARS patients. Recent studies regarding SARS and SARS-CoV have clarified that activation of mitogen-activated protein kinases (MAPKs) plays important roles in upregulation of cytokine expression and apoptosis both in vitro and in vivo. Both Akt and p38 MAPK are keys for determination of cell survival or death in SARS-CoV-infected cells in vitro. Agents being developed to target these signaling cascades may be important for the design of anti-SARS-CoV drugs. This review highlights recent progress regarding SARS-CoV biology, especially signal transduction in SARS-CoV-infected cells.
严重急性呼吸综合征(SARS)是一种新发现的传染病,由一种新型人类冠状病毒——SARS冠状病毒(SARS-CoV)引起。由于SARS患者的死亡率很高,了解SARS在体内和体外的病理机制对于预防SARS至关重要。SARS-CoV感染引起的信号通路激活导致下游分子的磷酸化和激活。在SARS患者中出现了两个相互冲突的细胞程序,即通过凋亡清除病毒感染细胞和通过产生抗病毒细胞因子延缓凋亡以存活。最近关于SARS和SARS-CoV的研究表明,丝裂原活化蛋白激酶(MAPKs)的激活在体外和体内细胞因子表达上调和凋亡中均起重要作用。Akt和p38 MAPK都是体外SARS-CoV感染细胞中决定细胞存活或死亡的关键因素。针对这些信号级联开发的药物可能对设计抗SARS-CoV药物很重要。本综述重点介绍了SARS-CoV生物学的最新进展,特别是SARS-CoV感染细胞中的信号转导。