Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
J Immunol. 2011 Jul 15;187(2):887-96. doi: 10.4049/jimmunol.1003737. Epub 2011 Jun 10.
Multiple receptors within the innate immune system have evolved to recognize nucleic acids as signatures of viral infection. It is believed that this specificity is essential for viral detection, as viruses often lack other invariant features that can serve as suitable targets for innate receptors. One such innate receptor, TLR9, has been implicated in the detection of many dsDNA viruses. In this study, we investigate the detection of murine gammaherpesvirus 68 (MHV68) by TLR9. We find that the genomic DNA of the murine CMV, a very potent inducer of innate responses. Genome-wide analysis of the number of stimulatory versus nonstimulatory CpG motifs present in the genome of each virus reveals that the MHV68 genome contains only a fraction of the number of immunostimulatory motifs present in murine CMV. Notably, MHV68 appears to have selectively suppressed the number of stimulatory motifs through cytosine to thymine conversion. These data suggest that certain viruses may have evolved and modified their genomic content to avoid recognition by nucleic acid-sensing receptors of the innate immune system.
先天免疫系统中的多种受体已进化为识别核酸，作为病毒感染的特征。人们认为这种特异性对于病毒检测至关重要，因为病毒通常缺乏其他可作为先天受体合适靶标的不变特征。TLR9 是一种先天受体，已被认为参与了许多 dsDNA 病毒的检测。在这项研究中，我们研究了 TLR9 对鼠γ疱疹病毒 68（MHV68）的检测。我们发现，鼠巨细胞病毒（一种非常有效的先天反应诱导物）的基因组 DNA 可以诱导 TLR9 识别。对每种病毒基因组中存在的刺激与非刺激 CpG 基序数量进行全基因组分析表明，MHV68 基因组中仅包含鼠巨细胞病毒中存在的免疫刺激性基序数量的一小部分。值得注意的是，MHV68 似乎通过胞嘧啶向胸腺嘧啶的转换选择性地抑制了刺激基序的数量。这些数据表明，某些病毒可能已经进化并修饰了其基因组内容，以避免被先天免疫系统的核酸感应受体识别。
