Chambers T J, Halevy M, Nestorowicz A, Rice C M, Lustig S
Department of Molecular Microbiology and Immunology, St Louis University School of Medicine, MO 63104, USA.
J Gen Virol. 1998 Oct;79 ( Pt 10):2375-80. doi: 10.1099/0022-1317-79-10-2375.
Several neuroinvasive and non-neuroinvasive West Nile (WN) viruses were characterized by nucleotide sequencing of their envelope (E) protein regions. Prolonged passage in mosquito cells caused loss of neuroinvasiveness and acquisition of an N-linked glycosylation site, which is utilized. Limited passage in cell culture also caused glycosylation but not attenuation, suggesting that glycosylation may not be directly responsible for attenuation and that a second mutation (L68 --> P) may also be involved. A monoclonal antibody-neutralization escape mutant with a substitution at residue 307, a site common to other flavivirus escape mutants, was also attenuated. A partially neuroinvasive revertant regained the parental E sequence, implying that determinants outside of the E region may also influence attenuation. Data suggest that the neuroinvasive determinants may be similar to those for other flaviviruses. Also, sequence comparison with the WN virus (Nigeria) strain revealed considerable divergence of the E protein at the nucleotide and amino acid levels.
通过对几种神经侵袭性和非神经侵袭性西尼罗河（WN）病毒包膜（E）蛋白区域进行核苷酸测序来对其进行特征分析。在蚊细胞中长时间传代导致神经侵袭性丧失并获得一个被利用的N - 连接糖基化位点。在细胞培养中有限传代也会导致糖基化，但不会导致减毒，这表明糖基化可能并非直接导致减毒，并且可能还涉及第二个突变（L68→P）。一个在307位残基处有替代的单克隆抗体中和逃逸突变体也出现了减毒，该位点是其他黄病毒逃逸突变体共有的位点。一个部分神经侵袭性回复株恢复了亲本E序列，这意味着E区域之外的决定因素也可能影响减毒。数据表明神经侵袭性决定因素可能与其他黄病毒的相似。此外，与西尼罗河病毒（尼日利亚）株的序列比较显示E蛋白在核苷酸和氨基酸水平上有相当大的差异。
