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

• 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
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21H02972/
• 关键词: ヒトヘルペスウイルス6; 内在性ウイルス; ヒトゲノム; 再活性化; 大規模解析; HHV-6; Endogenous virus; Disease association; WGS; ヘルペスウイルス; 内在性ウイルス様エレメント; 抗ウイルス免疫; テロメア; 潜伏感染

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.

我们在两个领域取得了进步。首先，我们使用来自英国生物库和所有US的新数据集进行了总共300,000个全基因组序列中内源性HHV-6的生物信息学筛查。这种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，并在内源性HHV-6和疾病之间找到新的关联。第二，我们开发了一种方法来通过PCR筛选内源性HHV-6。这使用了受试者的DNA的汇总，并允许我们在中间发射时通过PCR筛选内源性HHV-6。我们已经从大约3,000例心肌梗塞患者中筛选了内源性HHV-6。我们发现17例内源性HHV-6患者，患病率为0.57％。在17名内源性HHV-6阳性患者中，有6例HHV-6A患者为阳性，有10例患者，我们将进一步研究HHV-6的整合是否有助于冠状动脉疾病的进展。2023FY2023，我们将敲出内源性HHV-6的IPSC从IPSC中撤出内源性HHV-6进行疾病 - 疾病 - 疾病的疾病均不同。细胞表型。我们将总结到达现在获得的生物信息学分析的结果并作为论文发表。

项目成果

Potential involvement of endogenous HHV-6 in lymphangioleiomyomatosis

内源性 HHV-6 可能参与淋巴管平滑肌瘤病

• 发表时间: 2022
• 作者: Hayakawa K;Kojima S;Parrish NF.
• 通讯作者: Parrish NF.

Viruses make us who we are

病毒让我们成为现在的我们

• 发表时间: 2022
• 作者: 綿貫慎太郎;小林央;田久保圭誉;Parrish NF.
• 通讯作者: Parrish NF.