Takeda M, Sakaguchi T, Li Y, Kobune F, Kato A, Nagai Y
Institute of Medical Science, University of Tokyo, Shirokanedai 4-6-1, Tokyo, 108-0071, USA.
Virology. 1999 Apr 10;256(2):340-50. doi: 10.1006/viro.1999.9643.
The only complete genome nucleotide sequences of measles virus (MeV) reported to date have been for the Edmonston (Ed) strain and derivatives, which were isolated decades ago, passaged extensively under laboratory conditions, and appeared to be nonpathogenic. Partial sequencing of many other strains has identified >/=15 genotypes. Most recent isolates, including those typically pathogenic, belong to genotypes distinct from the Edmonston type. Therefore, the sequence of Ed and related strains may not be representative of those of pathological measles circulating at that or any time in human populations. Taking into account these issues as well as the fact that so many studies have been based upon Ed-related strains, we have sequenced the entire genome of a recently isolated pathogenic strain, 9301B. Between this recent isolate and the classical Ed strain, there were 465 nucleotide differences (2.93%) and 114 amino acid differences (2.19%). Computation of nonsynonymous and synonymous substitutions in open reading frames as well as direct comparisons of noncoding regions of each gene and extracistronic regulatory regions clearly revealed the regions where changes have been permissible and nonpermissible. Notably, considerable nonsynonymous substitutions appeared to be permissible for the P frame to maintain a high degree of sequence conservation for the overlapping C frame. However, the cause and the effect were largely unclear for any substitution, indicating that there is a considerable gap between the two strains that cannot be filled. The sequence reported here would be useful as a reference of contemporary wild-type MeV.
迄今为止报道的麻疹病毒(MeV)唯一完整的基因组核苷酸序列是针对埃德蒙斯顿(Ed)毒株及其衍生物的,这些毒株是几十年前分离出来的,在实验室条件下经过大量传代,且似乎无致病性。许多其他毒株的部分测序已鉴定出≥15种基因型。包括那些通常具有致病性的毒株在内,最近分离出的毒株大多属于与埃德蒙斯顿型不同的基因型。因此,Ed毒株及相关毒株的序列可能无法代表当时或人类群体中任何时期流行的致病性麻疹病毒的序列。考虑到这些问题以及许多研究都基于与Ed相关的毒株这一事实,我们对最近分离出的一株致病性毒株9301B的全基因组进行了测序。在这株近期分离出的毒株与经典的Ed毒株之间,存在465个核苷酸差异(2.93%)和114个氨基酸差异(2.19%)。对开放阅读框中的非同义替换和同义替换进行计算,以及对每个基因的非编码区和基因间调控区进行直接比较,清楚地揭示了哪些区域的变化是允许的,哪些是不允许的。值得注意的是,P阅读框似乎允许相当数量的非同义替换,以维持重叠的C阅读框的高度序列保守性。然而,任何替换的因果关系在很大程度上都不清楚,这表明这两种毒株之间存在相当大的差距,无法填补。本文报道的序列可作为当代野生型MeV的参考。