Laboratoire National de Santé, Institute of Immunology, Centre de Recherche Public-Santé/WHO Regional Reference, 20A rue Auguste Lumière, L-1950 Luxembourg, Luxembourg.
Virus Res. 2011 Jan;155(1):195-202. doi: 10.1016/j.virusres.2010.10.005. Epub 2010 Oct 13.
Differential effects of measles virus (MV) on the innate immune response may influence virus spread and severity of disease. Using a representative panel of 22 MV strains including 14 different genotypes, we found that wild-type (wt) differ considerably in their sensitivity to type I interferon (IFN). The wt virus production was 2-47-fold lower in IFN-alpha treated Vero/hSLAM cells, whereas vaccine virus production was reduced only 2-3-fold. Sequence analysis of the MV-P/C/V gene, revealed no obvious amino acid mutations that correlated with the different phenotypes. Strains also widely differed in their ability to induce type I IFN, tumor necrosis factor (TNF) alpha and other cytokines in human A549/hSLAM cells. Some wt strains that were highly sensitive to type I IFN induced only low levels of these and other cytokines. In vitro wt strains that produced the 5' copy-back defective interfering RNAs (5'cb-diRNA) characterized by Shingai et al. (2007), induced high levels of cytokines that otherwise were only reached by vaccine strains. These 5'cb-diRNAs emerged only in virus cultures during multiple passaging and were not detectable in clinical samples of measles patients. These subgenomic RNAs are an important confounding parameter in passaged wt viruses which must be carefully assessed in all in vitro studies. The present data show that MV wt strains differ in their sensitivity and their ability to temper with the innate immune response, which may result in differences in virulence.
麻疹病毒（MV）对先天免疫反应的差异影响可能会影响病毒的传播和疾病的严重程度。使用包括 14 种不同基因型的 22 种 MV 株的代表性小组，我们发现野生型（wt）在对 I 型干扰素（IFN）的敏感性方面存在很大差异。在 IFN-α处理的 Vero/hSLAM 细胞中，wt 病毒的产量降低了 2-47 倍，而疫苗病毒的产量仅降低了 2-3 倍。MV-P/C/V 基因的序列分析未显示出与不同表型相关的明显氨基酸突变。这些毒株在诱导人 A549/hSLAM 细胞中的 I 型 IFN、肿瘤坏死因子（TNF）α和其他细胞因子的能力方面也存在广泛差异。一些对 I 型 IFN 高度敏感的 wt 株仅诱导这些和其他细胞因子的低水平。在体外，产生 Shingai 等人（2007 年）所描述的 5' 回文缺陷干扰 RNA（5'cb-diRNA）的 wt 株诱导高水平的细胞因子，而这些细胞因子仅由疫苗株达到。这些 5'cb-diRNAs 仅在病毒传代培养期间出现，而在麻疹患者的临床样本中无法检测到。这些亚基因组 RNA 是传代 wt 病毒的一个重要混杂参数，在所有体外研究中都必须仔细评估。本研究数据表明，MV wt 株在敏感性和调节先天免疫反应的能力方面存在差异，这可能导致毒力的差异。
