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

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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.