Single-cell RNA sequencing analysis of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20756
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0803:Pathology, infection/immunology, and related fields
• Research Institution: Nagoya University
• Principal Investigator: Suzuki Takako 名古屋大学, 医学部附属病院, 医員 (60908721)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: EBウイルス関連血球貪食性リンパ組織球症 / シングルセルシーケンス / Epstein-Barr virus / 伝染性単核症

Outline of Final Research Achievements

In this study, we applied single-cell RNA sequencing technology to characterize the gene expression of the epidemic cell population of EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and compared it with infectious mononucleosis (EBV-IM), a typical clinical manifestation of primary EBV infection. Three pediatric patients with EBV-HLH, 2 patients with EBV-IM and 2 healthy adults were enrolled, and peripheral blood mononuclear cells were analyzed. A total of 37,405 cells were included. In EBV-HLH, genes involved in type Ⅰ interferon signaling were commonly upregulated in each cell fraction, while monocytes showed robust changes in genes expression in all three EBV-HLH cases. The distinct proliferative CD8+ T cell cluster was recognized in the acute phase of EBV-IM, which cluster was scarce in all three EBV-HLH cases. The gene-expression profile obtained for this cluster is an important finding for understanding the immune response to EBV infection.

Free Research Field

小児感染症

Academic Significance and Societal Importance of the Research Achievements

EBウイルス（EBV）は世界に普遍的に存在するウイルスだが、その感染により時に伝染性単核症（EBV-IM）を発症し、さらに稀にEBV関連血球貪食性リンパ組織球症（EBV-HLH）という重篤な疾患を発症する。これらのEBV感染性疾患の詳細なメカニズムは十分に解明されていない。EBV-HLHの治療標的としてⅡ型インターフェロン（IFN）が着目されてきたが、本研究ではⅠ型IFNシグナリングの関与が示され、新たな治療標的の可能性を示唆した。また、EBV-IMに特異的に出現が確認されたCD8陽性T細胞クラスタの遺伝子発現プロファイルは、EBV感染に対する免疫応答を理解する上で重要な知見と考えられた。