Demethylation around the transcriptional start site of the IFN-β gene induces IFN-β production and protection against influenza virus infection
Demethylation around the transcriptional start site of the IFN-β gene induces IFN-β production and protection against influenza virus infection
复制标题
IFN-β 基因转录起始位点周围的去甲基化可诱导 IFN-β 的产生并预防流感病毒感染
DOI：
10.1016/j.bbrc.2019.09.136
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发表时间：
2019
影响因子：
3.1
通讯作者：
Nakaya Takaaki
中科院分区：
文献类型：
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作者：
Nishioka Keisuke;Daidoji Tomo;Nakaya Takaaki
季节性流感与生活方式相关的风险因素有关，有人认为个体的表观遗传状态在感染的严重程度中起着重要作用。众所周知，表观遗传学严格调节每个组织中的基因表达，并且异常的表观遗传状态可以影响疾病的发展。尽管有一些研究，但关于流感病毒感染前后表观遗传状态变化的信息有限;特别是，不知道特定部位的表观遗传状态是否会影响随后的感染。在这里，我们分析了CpG甲基化状态的克隆来源于人类原发性小气道上皮细胞具有相同的遗传背景，但不同的病毒复制率。我们的研究表明，使用CRISPR/dCas 9系统对IFN-β转录起始位点下游的CpG进行去甲基化可以抑制随后流感病毒感染期间的病毒复制。因此，我们的观察表明，表观基因组编辑可能提供足够的保护，以抵御流感病毒。
Seasonal influenza is related to lifestyle-associated risk factors and it has been suggested that the epigenetic state of the individual plays an important role in the severity of infection. It is well known that epigenetics stringently regulate gene expression in each tissue and that aberrant epigenetic states can influence disease development. Despite some studies, limited information is available on changes in epigenetic states before and after influenza virus infection; in particular, it is unknown whether the epigenetic state at specific sites affects subsequent infection. Here, we analyzed CpG methylation states in clones derived from human primary small airway epithelial cells with the same genetic background but different viral replication rates. Our study revealed that demethylating CpGs downstream of theIFN-βtranscription start site using a CRISPR/dCas9 system suppressed viral replication during subsequent influenza virus infection. Thus, our observations suggest that epigenome editing might provide adequate protection against the influenza virus.