A highly attenuated rabies virus HEP-Flury strain reverts to virulent by single amino acid substitution to arginine at position 333 in glycoprotein
A highly attenuated rabies virus HEP-Flury strain reverts to virulent by single amino acid substitution to arginine at position 333 in glycoprotein
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DOI：
10.1016/j.virusres.2006.01.014
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发表时间：
2006-08-01
期刊：
影响因子：
5
通讯作者：
Morimoto, Kinjiro
中科院分区：
文献类型：
--
作者：
Takayama-Ito, Mutsuyo;Inoue, Ken-ichi;Morimoto, Kinjiro
几个固定的狂犬病病毒株的糖蛋白中第333位的氨基酸是导致成年小鼠致病的原因。精氨酸在这一位置的替代极大地降低了成年小鼠的病毒致病性。通过使用单抗选择的逃逸突变体和反向遗传学产生的点突变病毒，已经建立了这种单一氨基酸替代的减毒作用。一种高度减毒的Hep-Flury菌株，在细胞培养中通过连续传代选择，在这个位置含有谷氨酰胺。在这项研究中，产生了一个点突变的rHEp(333)R病毒，在第333位含有精氨酸，并检测了这种替换在狂犬病致病中的作用。RHEp(333)R具有在小鼠脑内扩散和繁殖的能力，而亲本rHEP则没有。RHEp(333)R脑内接种对成年小鼠的致病性明显增强。我们证实，在高度减毒的Hep-Flury菌株中，第333位的精氨酸有助于致病性的逆转。(C)2006爱思唯尔B.V.保留所有权利。
An amino acid at position 333 in the glycoprotein of several fixed rabies virus strains is responsible for the pathogenicity in adult mice. Substitution of arginine at this position largely reduces the viral pathogenicity in adult mice. Attenuation by this single amino acid substitution has been established by using escape mutants selected by monoclonal antibodies and point-mutated virus generated by reverse-genetics. A highly attenuated HEP-Flury strain, which was selected by serial passages in cell cultures, has glutamine at this position. In this study, a point-mutated rHEp(333)R virus, having arginine at position 333, was generated and examined for the responsibility of this substitution in rabies pathogenicity. The rHEp(333)R acquired an ability to spread and propagate in mouse brain but the parental rHEP did not. The pathogenicity of rHEp(333)R to adult mice by intracerebral inoculation largely increased. We confirmed that an arginine at position 333 contributed to reversion of the pathogenicity in a highly attenuated HEP-Flury strain. (c) 2006 Elsevier B.V. All rights reserved.