Wild type measles virus attenuation independent of type I IFN.
Wild type measles virus attenuation independent of type I IFN.
复制标题
野生型麻疹病毒衰减独立于I型IFN。
DOI：
10.1186/1743-422x-5-22
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发表时间：
2008-02-03
期刊：
影响因子：
4.8
通讯作者：
Wild, Fabian T.
中科院分区：
文献类型：
--
作者：
Druelle, Johan;Sellin, Caroline I.;Waku-Kouomou, Diane;Horvat, Branka;Wild, Fabian T.
麻疹病毒减毒历来是通过适应细胞培养来进行的。目前的教条是，减毒病毒株比野生型（wt）诱导更多的I型干扰素，并且对干扰素诱导的保护作用更有抵抗力。麻疹病毒分离株（G954-PBL）在Vero细胞上传代13代后，在体内产生了强烈的减毒作用。适应病毒（G954-V13）与其亲本株仅5个氨基酸不同（P/V/C中4个和M基因中1个）。虽然疫苗株Edmonston Zagreb可以在各种灵长类动物细胞中同样良好地复制，但两种G954菌株均表现出对最初用于其繁殖的特定细胞类型的限制。令人惊讶的是，我们观察到两种G954菌株都诱导I型IFN，wt菌株诱导的IFN甚至比减毒菌株更多，特别是在人浆细胞样树突状细胞中。I型IFN诱导的保护免受两种G954菌株的感染取决于所分析的细胞类型，在用于生长病毒株的细胞中效率较低。因此，M和P/V/C蛋白的突变可以严重影响MV的致病性、细胞嗜性，并导致病毒减毒而不干扰α/β IFN系统。
Measles virus attenuation has been historically performed by adaptation to cell culture. The current dogma is that attenuated virus strains induce more type I IFN and are more resistant to IFN-induced protection than wild type (wt). The adaptation of a measles virus isolate (G954-PBL) by 13 passages in Vero cells induced a strong attenuation of this strain in vivo. The adapted virus (G954-V13) differs from its parental strain by only 5 amino acids (4 in P/V/C and 1 in the M gene). While a vaccine strain, Edmonston Zagreb, could replicate equally well in various primate cells, both G954 strains exhibited restriction to the specific cell type used initially for their propagation. Surprisingly, we observed that both G954 strains induced type I IFN, the wt strain inducing even more than the attenuated ones, particularly in human plasmacytoid Dendritic Cells. Type I IFN-induced protection from the infection of both G954 strains depended on the cell type analyzed, being less efficient in the cells used to grow the viral strain. Thus, mutations in M and P/V/C proteins can critically affect MV pathogenicity, cellular tropism and lead to virus attenuation without interfering with the α/β IFN system.