Lobigs M
Division of Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra, A.C.T.
Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6218-22. doi: 10.1073/pnas.90.13.6218.
Flavivirus protein biosynthesis involves the proteolytic processing of a single polyprotein precursor by host- and virus-encoded proteinases. In this study, the requirement for the proteolytic function of the viral proteinase NS3 for correct processing of a polyprotein segment encompassing the Murray Valley encephalitis virus structural proteins is shown. The NS3-mediated cleavage in the structural polyprotein region presumably releases the capsid protein from its membrane anchor and triggers the appearance of the premembrane (prM) protein. This suggests that cleavage of prM by signal peptidase in the lumen of the endoplasmic reticulum is under control of a cytoplasmic cleavage catalyzed by a viral proteinase. The function of the viral proteinase is also essential for secretion of flaviviral spike proteins when expressed from cDNA via vaccinia virus recombinants or in COS cell transfections. This has important implications for the design of flavivirus subunit vaccines.
黄病毒的蛋白质生物合成涉及由宿主和病毒编码的蛋白酶对单一多蛋白前体进行蛋白水解加工。在本研究中，展示了病毒蛋白酶NS3的蛋白水解功能对于正确加工包含墨累谷脑炎病毒结构蛋白的多蛋白片段的必要性。结构多蛋白区域中由NS3介导的切割可能会将衣壳蛋白从其膜锚定处释放出来，并引发前膜（prM）蛋白的出现。这表明内质网腔中信号肽酶对prM的切割受病毒蛋白酶催化的细胞质切割的控制。当通过痘苗病毒重组体从cDNA表达或在COS细胞转染中表达时，病毒蛋白酶的功能对于黄病毒刺突蛋白的分泌也是必不可少的。这对黄病毒亚单位疫苗的设计具有重要意义。
