Leparc-Goffart I, Hingley S T, Jiang X, Chua M M, Lavi E, Weiss S R
Department of Microbiology, University of Pennsylvania, Philadelphia 19104, USA.
Adv Exp Med Biol. 1998;440:627-33. doi: 10.1007/978-1-4615-5331-1_81.
C12, an attenuated, fusion defective, very weakly hepatotropic mutant of MHV-A59 has been further characterized. Analysis of C12 in vivo in C57BL/6 mice has shown that despite the fact that this virus replicates in the brain to titers at least as high as wild type and causes acute encephalitis similar to wild type, this virus causes minimal demyelination. Thus acute encephalitis is not sufficient for induction of demyelination by wild type MHV-A59. We have previously shown that C12 has two amino acid substitutions relative to wild type virus in the spike gene, Q159L (in the receptor binding domain of S1) and H716D (in the signal sequence for cleavage of S). We have now sequenced the rest of the 31 kb genome of C12 and compared it to wild type virus. Only three additional amino acids substitutions were found, all within the replicase gene, one in the predicted papain like proteinase (PLP)-2 domain and one in the predicted helicase domain. Thus, determinants of virulence, hepatotropism, and demyelination may map to the replicase gene as well as to the spike gene.
C12是MHV - A59的一种减毒、融合缺陷且肝嗜性非常弱的突变体，已得到进一步鉴定。对C57BL / 6小鼠体内的C12进行分析表明，尽管这种病毒在脑中复制的滴度至少与野生型一样高，并引起与野生型相似的急性脑炎，但这种病毒导致的脱髓鞘现象极少。因此，急性脑炎不足以诱导野生型MHV - A59引发脱髓鞘。我们之前已经表明，相对于野生型病毒，C12在刺突基因中有两个氨基酸替换，即Q159L（在S1的受体结合结构域中）和H716D（在S的裂解信号序列中）。我们现在对C12的31 kb基因组的其余部分进行了测序，并将其与野生型病毒进行了比较。仅发现另外三个氨基酸替换，均在复制酶基因内，一个在预测的类木瓜蛋白酶（PLP）- 2结构域中，一个在预测的解旋酶结构域中。因此，毒力、肝嗜性和脱髓鞘的决定因素可能定位于复制酶基因以及刺突基因。
