Radecke F, Billeter M A
Institut für Molekularbiologie, Abteilung 1, Universität Zürich, Hönggerberg, Switzerland.
Virology. 1996 Mar 1;217(1):418-21. doi: 10.1006/viro.1996.0134.
Measles virus (MV) is a highly contagious agent which causes a major health problem in developing countries. Efficacious and safe live attenuated vaccine strains are available, but for the elimination of measles a better knowledge about the molecular biology of MV appears crucial. Whereas the roles of the six structural proteins in the replication cycle are known, the functions of the two nonstructural proteins C and V are unclear, which is also true for related viruses. In vitro studies implicating Sendai virus suggest that the C protein might be involved in downregulating viral mRNA synthesis (J. Curran, J.B. Marq, and D. Kolakofsky, Virology 189, 647-656, 1992). However, not all members of the Paramyxovirinae subfamily encode this protein, raising the question about its importance for the viral replication cycle. Taking advantage of a recently developed reverse genetics system allowing MV recovery from cloned DNA (F. Radecke, P. Spielhofer, H. Schneider, K. Kaelin, M. Huber, C. Dötsch, G. Christiansen, and M.A. Billeter, EMBO J. 14, 5773-5784, 1995), the question was addressed whether the C protein is essential for the life cycle of MV. A plasmid was constructed to produce a derivative of the Edmonston B vaccine strain, MV C- EdB, having its C reading frame silenced by two point mutations. The C- mutant MV could indeed be rescued, and it multiplies in cultured cells without obvious impairment.
麻疹病毒(MV)是一种极具传染性的病原体,在发展中国家引发了重大的健康问题。目前已有有效且安全的减毒活疫苗株,但要消除麻疹,似乎关键在于更深入地了解MV的分子生物学。虽然已知六种结构蛋白在复制周期中的作用,但两种非结构蛋白C和V的功能尚不清楚,相关病毒亦是如此。涉及仙台病毒的体外研究表明,C蛋白可能参与下调病毒mRNA的合成(J. Curran、J.B. Marq和D. Kolakofsky,《病毒学》189卷,647 - 656页,1992年)。然而,副粘病毒亚科并非所有成员都编码这种蛋白,这就引发了关于其对病毒复制周期重要性的疑问。利用最近开发的一种反向遗传学系统,该系统可从克隆DNA中拯救出MV(F. Radecke、P. Spielhofer、H. Schneider、K. Kaelin、M. Huber、C. Dötsch、G. Christiansen和M.A. Billeter,《欧洲分子生物学组织杂志》14卷,5773 - 5784页,1995年),研究了C蛋白对MV生命周期是否必不可少这一问题。构建了一个质粒以产生埃德蒙斯顿B疫苗株的衍生物MV C - EdB,其C阅读框因两个点突变而沉默。C突变型MV确实能够被拯救出来,并且它在培养细胞中增殖,没有明显受损。