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为探索脊灰病毒型内重组、位点突变等分子特征与神经毒力的关系,对2002年6月四川省攀枝花地区发生的急性弛缓性麻痹(acute flaccid paralysis,AFP)聚集病例的分离病毒株进行了转基因小鼠(PVR-Tg21 mice)神经毒力实验和全基因组核苷酸序列测定。结果显示:所测4株分离病毒(均为Ⅱ型脊灰病毒)神经毒力没有明显升高。4株病毒基因全长都是7 439bp,编码区翻译的氨基酸全长2 207aa。4株病毒的VP1区核苷酸序列完全相同。6208和6235c两株病毒是由Ⅱ型和Ⅲ型脊灰病毒在3A区重组而来,6209和6236两株病毒是由Ⅱ型和Ⅰ型脊灰病毒在2C区重组而来。4株病毒在5’非编码区nt481和VP1区的nt2 909两个强减毒位点都发生回复突变,6209和6236两株病毒重组的SabinⅠ的重要减毒位点nt6 203亦发生回复突变。结合神经毒力实验和序列分析结果可以确定脊灰病毒的型别间的重组与神经毒力没有直接关系,同时可以推论SabinⅢ的nt5 832,SabinⅡ的nt1 450和nt2 386这3个位点可能是毒力相关位点。
In order to explore the relationship between the molecular characteristics of poliovirus type recombination and site mutation and neurotoxicity, the isolation of the isolated strains of acute flaccid paralysis (AFP) in Panzhihua, Sichuan Province in June 2002 The neurotoxicity test and genome-wide nucleotide sequence determination of transgenic mice (PVR-Tg21 mice) were performed. The results showed that there was no significant increase in the virulence of the four isolates (all poliovirus type Ⅱ). The total length of the 4 strains of viruses was 7 439 bp, and the translated amino acid in the coding region was 2 207 aa. The VP1 region of the four viruses has the same nucleotide sequence. The two viruses, 6208 and 6235c, were recombined by type II and type III poliovirus in region 3A, and the two viruses 6209 and 6236 were recombined in type 2 by type II and type I poliovirus. Four strains of viruses were found to be back-mutated in two strong attenuated sites, nt481 in the 5 ’non-coding region and nt2 909 in the VP1 region, and a retroviral mutation was also found in nt6 203, an important site of Sabin I recombination in the two strains of 6209 and 6236. Combined with the results of neurovirulence experiments and sequence analysis, it was confirmed that the recombination between poliovirus types was not directly related to neurovirulence. At the same time, it can be inferred that the three sites of nt5 832 of Sabin Ⅲ, nt1 450 of Sabin Ⅱ and nt2 386 may be Toxicity related sites.