Neuroblastoma cell-adapted yellow fever virus: mutagenesis of the E protein locus involved in persistent infection and its effects on virus penetration and spread.
Neuroblastoma cell-adapted yellow fever virus: mutagenesis of the E protein locus involved in persistent infection and its effects on virus penetration and spread.
复制标题
神经母细胞瘤细胞适应的黄热病病毒：参与持续感染的 E 蛋白位点的突变及其对病毒渗透和传播的影响。
DOI：
10.1099/vir.0.80314-0
复制
发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Chambers,ThomasJ
中科院分区：
文献类型：
--
作者：
Vlaycheva,Leonssia;Nickells,Michael;Droll,DeborahA;Chambers,ThomasJ
用黄热病17 D病毒持续感染小鼠神经母细胞瘤NB 41 A3细胞产生病毒变体，其表现出有缺陷的细胞穿透、差的细胞间扩散、小的空斑尺寸和降低的生长效率，这是由包膜蛋白中位置360和362处的甘氨酸取代天冬氨酸或谷氨酸引起的。这些位置出现在电荷簇Asp 360-Asp 361-Glu 362内，位于结构域III中，靠近其与结构域I的界面。为了进一步表征变异表型的分子基础，研究了一系列在位置360、361和362处含有取代的突变病毒对神经母细胞瘤适应性变异体的典型细胞培养特性的影响。在位置360处的大多数取代产生在细胞穿透、生长效率和细胞间传播方面非常缺陷的病毒，而用谷氨酸取代产生与亲本黄热病17 D无区别的病毒。用赖氨酸取代是不耐受的，用天冬酰胺取代导致频繁的野生型回复突变体。甘氨酸残基在361位是不容许的，但在362位的取代产生了小噬斑病毒，类似于在360位取代的效果。这些数据表明，黄热病毒E蛋白在结构域III内包含一个位点，其中负电荷簇对于该结构域在病毒附着阶段之后的病毒-细胞相互作用中的最佳功能非常重要。模型预测表明，突变改变了局部性质的循环内域III，并可能损害相互作用的结构域I的相邻区域的结构域在构象变化，发生在E蛋白与病毒进入。
Persistent infection of mouse neuroblastoma NB41A3 cells with yellow fever 17D virus generates viral variants which exhibit defective cell penetration, poor cell-to-cell spread, small plaque size and reduced growth efficiency, caused by substitution of glycine for aspartic acid or glutamic acid at positions 360 and 362 in the envelope protein. These positions occur within a charge cluster, Asp360-Asp361-Glu362, located in domain III, near its interface with domain I. To characterize further the molecular basis for the variant phenotype, a series of mutant viruses containing substitutions at position 360, 361 and 362, were studied for effects on the cell culture properties typical of the neuroblastoma-adapted variant. Most substitutions at position 360 gave rise to viruses that were very defective in cell penetration, growth efficiency and cell-to-cell spread, whereas substitution with glutamic acid yielded a virus indistinguishable from parental yellow fever 17D. Substitution with lysine was not tolerated and substitution with asparagine resulted in frequent wild-type revertants. A glycine residue was not tolerated at position 361, but substitution at 362 yielded a small plaque virus, similar to the effect of substitution at position 360. These data indicate that the yellow fever virus E protein contains a locus within domain III where a negative-charge cluster is important for optimal function of this domain in virus-cell interactions beyond the stage of virus attachment. Modelling predictions suggest that the mutations alter the local properties of the loop within domain III, and may compromise interactions of this domain with an adjacent region of domain I during conformational changes that occur in the E protein in association with virus entry.
使用与黄热病 E 蛋白序列相对应的合成肽生产病毒特异性抗血清：简要报告。
影响因子：
2.2
作者：
R. Jackson;R. Phillpotts
通讯作者：
R. Phillpotts
影响因子：
56.9
作者：
RICE, CM;LENCHES, EM;STRAUSS, JH
通讯作者：
STRAUSS, JH
蜱传脑炎病毒 II 类病毒融合蛋白 E 膜相关三聚体低 pH 诱导形式的表征及其结晶
影响因子：
5.4
作者：
K. Stiasny;S. Bressanelli;J. Lepault;F. Rey;F. Heinz
通讯作者：
F. Heinz