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ヘルペスウイルスのゲノムへの組み込みと再活性化: 大規模解析から探る疾患との関連

疱疹病毒整合到基因组中并重新激活：通过大规模分析探索与疾病的关系

基本信息

批准号：
21H02972
负责人：
Parrish Nicholas
金额：
$ 10.98万
依托单位：
Institute of Physical and Chemical Research
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2021
资助国家：
日本
起止时间：
2021-04-01 至 2025-03-31
项目状态：
未结题

项目摘要

We have made progress in two areas.First, we expanded our bioinformatic screening for endogenous HHV-6 in a total of 300,000 whole genome sequences using new datasets from UK biobank and All-of-Us. This screening will allow us to reveal the global association of endogenous HHV-6-positive subjects and find new associations between endogenous HHV-6 and disease.Second, we have developed a method to screen endogenous HHV-6 by PCR. This uses the pooling of subjects’ DNA and allows us to screen endogenous HHV-6 by PCR at middle-throughput. We already screened for endogenous HHV-6 from approximately 3,000 patients with myocardial infarction. We found 17 patients with endogenous HHV-6, with a prevalence of 0.57%. Out of 17 endogenous HHV-6-positive patients, 6 patients were positive for HHV-6A, 10 patients were positive for HHV-6B, and 1 patient was positive for solo-DR form of HHV-6B. We will further investigate if HHV-6 integration contributes to the progression of coronary artery disease.In FY2023, we will knock out endogenous HHV-6 from iPSCs carrying endogenous HHV-6 to investigate the disease associations. We will differentiate the cells and test if endogenous HHV-6 would change the cellular phenotype. We will summarize the results of bioinformatic analysis obtained up to now and publish as a paper.

我们在两个方面取得了进展。首先，我们利用英国生物库和All-of-Us的新数据集，在总共30万个全基因组序列中扩大了对内源性HHV-6的生物信息学筛选。这项筛查将使我们能够揭示内源性HHV-6阳性受试者的全球关联，并发现内源性HHV-6与疾病之间的新关联。第二，我们建立了一种通过聚合酶链式反应筛查内源性HHV-6的方法。这使用了受试者DNA的池，并允许我们通过中等吞吐量的PCR来筛查内源性HHV-6。我们已经对大约3000名心肌梗塞患者进行了内源性HHV-6的筛查。我们发现了17例内源性HHV-6，患病率为0.57%。在17例内源性HHV-6阳性患者中，6例HHV-6A阳性，10例HHV-6B阳性，1例单DR阳性。我们将进一步研究HHV-6整合是否有助于冠状动脉疾病的进展。在2023财年，我们将从携带内源性HHV-6的IPSCs中敲除内源性HHV-6，以研究疾病的相关性。我们将对细胞进行分化，并测试内源性HHV-6是否会改变细胞表型。我们将总结目前生物信息学分析的结果，并以论文形式发表。