摘要
为了解乙脑减毒活疫苗株SA14 14 2的神经毒力减毒机制 ,用RT PCR方法分别扩增不同减毒程度毒株的E基因 ,克隆、测序 ,继而对各毒株序列进行比较。结果表明SA14 强毒株与SA14 12 1 7株间只有 3个氨基酸发生改变 (E 10 7,E 176 ,E 4 39) ,SA14 12 1 7与SA14 9 7和SA14 5 3株间有另 3个氨基酸发生改变 (E 138,E 2 79,E 315 )。SA14 9 7株与SA14 5 3株只有一个核苷酸NT 4 0 5不同 ,但未引起氨基酸改变。SA14 14 2疫苗株除保留SA14 12 1 7和SA14 9 7所改变的 6个氨基酸外 ,另有 2个氨基酸发生了改变 (E 177,E 2 6 4 ) ,共计在E区共发生 8个氨基酸的替代。SA14 12 1 7株的低神经毒力很不稳定而其余各株的弱毒特征很稳定。因此 ,E 176 (Ile→Val) ,E 4 39(Lys→Arg)和E 10 7(Leu→Phe)可能与神经外和神经内毒力减弱有关。E 138(Gul→Lys) ,E 315 (Ala→Val)和E 2 79(Lys→Met)
For understanding the mechanism of neurovirulence attenuation of the Japanese encephalitis virus(JEV),nucleotides of the E coding region of five JE strains,one wild and four attenuated viruses,were amplified by PCR and sequenced.A comparison of the five sequences indicated that there were totally twelve nucleotides and eight amino acid differences between the vaccine strain SA\-\{14\} 14 2(PHK 8) and its parent SA14,in which three amino acids(E 107,E 176,E 439) were different between SA14 and SA\-\{14\} 12 1 7,and other three amino acids(E 138,E 279,E 315) were different between SA\-\{14\} 12 1 7 and SA\-\{14\} 9 7 as well as SA\-\{14\} 5 3.The SA\-\{14\} 12 1 7 strain showed low neurovirulence but unstable,whereas all the other attenuated strains showed high stability of attenuation.Our results suggest that the mutations of E 176(Ile→Val),E 439(Lys→Arg) and E 107(Leu→Phe) may contribute for the attenuation of neuroinvasion and neurovirulence and the mutations of E 138,E 279,E 315 may contribute to the attenuation of the neurovirulence and its stability.
出处
《中国病毒学》
CSCD
2002年第3期216-220,共5页
Virologica Sinica
