MAPPING OF MUTATIONS ASSOCIATED WITH NEUROVIRULENCE IN MONKEYS INFECTED WITH SABIN 1 POLIOVIRUS REVERTANTS SELECTED AT HIGH-TEMPERATURE
MAPPING OF MUTATIONS ASSOCIATED WITH NEUROVIRULENCE IN MONKEYS INFECTED WITH SABIN 1 POLIOVIRUS REVERTANTS SELECTED AT HIGH-TEMPERATURE
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DOI：
10.1128/jvi.64.10.4922-4929.1990
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发表时间：
1990-10-01
影响因子：
5.4
通讯作者：
HORAUD, F
中科院分区：
文献类型：
--
作者：
CHRISTODOULOU, C;COLBEREGARAPIN, F;HORAUD, F
脊髓灰质炎病毒1型神经毒力难以分析，因为有56个突变将神经毒力Mahoney毒株与减毒Sabin毒株区分开来。我们已经分离了四种神经毒性突变体，它们与温度敏感亲本Sabin 1菌株的差异仅在于几个突变，使用温度抗性选择：突变体S137C1在37.5 ℃分离。在38.5 ℃下分离S138C5。在39.5 ℃下分离S139C6和S139C10。C.所有四个突变体在超最适温度下都具有正的繁殖能力（Rct+表型）。突变体S137C1在四只食蟹猴中的两只中诱导瘫痪，并且另外三种突变体在四只猴子中的四只中诱导瘫痪。从S137C1突变体到S139突变体，病变评分增加。为了绘制与耐热性和神经毒力相关的突变，我们对Sabin 1基因组与Mahoney基因组不同的所有区域进行了测序。S137C1突变体在5“非编码区和3”非编码区各有一个突变。突变体S138C5具有这些突变以及3D聚合酶基因中的另一个突变。S139突变体在衣壳蛋白区有三个额外的突变。这些突变位于Sabin 1和Mahoney基因组不同的位置，除了5“非编码区的突变。非编码区的突变，显然赋予低程度的神经毒力。S138 C5和S139突变体与S137 C1不同的3D聚合酶突变可能是S138 C5和S139突变体具有高神经毒力的原因。S139突变体的神经毒力最高，可能与衣壳区突变有关。
Poliovirus type 1 neurovirulence is difficult to analyze because of the 56 mutations which differentiate the neurovirulent Mahoney strain from the attenuated Sabin strain. We have isolated four neurovirulent mutants which differ from the temperature-sensitive parental Sabin 1 strain by only a few mutations, using selection for temperature resistance: mutant S137C1 was isolated at 37.5.degree. C, S138C5 was isolated at 38.5.degree. C, and S139C6 and S139C10 were isolated at 39.5.degree. C. All four mutants had a positive reproductive capacity at supraoptimal temperature (Rct+ phenotype). Mutant S137C1 induced paralysis in two of four cynomolgus monkeys, and the three other mutants induced paralysis in four of four monkeys. The lesion score increased from the S137C1 mutant to the S139 mutants. To map the mutations associated with thermoresistance and neurovirulence, we sequenced all regions in which the Sabin 1 genome differs from the Mahoney genome. The S137C1 mutant had one mutation in the 5'' noncoding region and another in the 3'' noncoding region. Mutant S138C5 had these mutations plus another mutation in the 3D polymerase gene. The S139 mutants had three additional mutations in the capsid protein region. The mutations were located at positions at which the Sabin 1 and the Mahoney genomes differ, except for the mutation in the 5'' noncoding region. The noncoding-region mutations, apparently confer a low degree of neurovirulence. The 3D polymerase mutation, which distinguishes S138C5 and S139 mutants from S137C1, is probably responsible for the high neurovirulence of S138C5 and S139 mutants. The capsid region mutations may contribute to the neurovirulence of the S139 mutants, which was the highest among the mutants.