ROLE OF MUTATIONS G-480 AND C-6203 IN THE ATTENUATION PHENOTYPE OF SABIN TYPE-1 POLIOVIRUS
ROLE OF MUTATIONS G-480 AND C-6203 IN THE ATTENUATION PHENOTYPE OF SABIN TYPE-1 POLIOVIRUS
复制标题
DOI：
10.1128/jvi.69.12.7601-7605.1995
复制
发表时间：
1995-12-01
影响因子：
5.4
通讯作者：
ALMOND, JW
中科院分区：
文献类型：
--
作者：
MCGOLDRICK, A;MACADAM, AJ;ALMOND, JW
在区分1型脊髓灰质炎病毒疫苗株（Sabin 1）与其神经毒性祖株（P1/Mahoney）的55个点突变中，先前的研究强烈暗示有两个点突变是衰减表型的决定因素。位于5'非编码区480位的A变为G被认为是主要的减毒突变，类似于2型和3型脊髓灰质炎病毒分别在481和472位的突变。此外，6203位U到C的变化，导致聚合酶蛋白3D的氨基酸变化，也被认为是衰减的决定因素，尽管程度较小。为了评估这些突变对衰减和温度敏感性的贡献，在Sabin 1和P1/Mahoney的感染性cDNA克隆中，这些位置产生了互变。组织培养和灵长类动物实验表明，这两个突变对Sabin 1菌株的温度敏感性有一定的贡献，但都不是衰减的强烈决定因素。
Of the 55 point mutations which distinguish the type 1 poliovirus vaccine strain (Sabin 1) from its neurovirulent progenitor (P1/Mahoney), two have been strongly implicated by previous studies as determinants of the attenuation phenotype. A change of an A to a G at position 480, located within the 5' noncoding region, has been suggested to be the major attenuating mutation, analogous to the mutations at positions 481 and 472 in poliovirus types 2 and 3, respectively. In addition, the change of a U to a C at position 6203, resulting in an amino acid change in the polymerase protein 3D, has also been implicated as a determinant of attenuation, albeit to a lesser extent. To assess the contributions of these mutations to attenuation and temperature sensitivity, reciprocal changes were generated at these positions in infectious cDNA clones of Sabin 1 and P1/Mahoney. Assays in tissue culture and primates indicated that the two mutations make some contribution to the temperature sensitivity of the Sabin 1 strain but that neither is a strong determinant of attenuation.