The mechanism of cell-contact mediated viral reactivation and search for its inhibitors

2022 Fiscal Year Final Research Report

• Project/Area Number: 17K08869
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Kanno Takayuki 国立感染症研究所, 感染病理部, 主任研究官 (50272563)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Keywords: カポジ肉腫 / 細胞間接触 / 再活性化 / cell-to-cell感染 / Hypoxiaシグナル伝達系

Outline of Final Research Achievements

To investigate the mechanism of cell-contact-mediated viral reactivation of KSHV, a co-culture experiment was conducted involving adherent cells and PEL cells, with or without the use of Transwell equipment. HeLa and HEK293 cells were cultured as adherent cells, while TY-1, BCBL-1, and Spel cells were cultured as KSHV-infected B cells. Bjab cells were utilized as KSHV non-infected B cells for control purposes. Total RNA was subsequently extracted. Transcriptome and gene ontology analysis revealed distinct functional enrichment of genes related to hypoxia signaling. Importantly, this finding was consistent across different adherent cell types and independent of the KSHV infection status in the B cells. Thus, the cell contact between adherent cells and B cells induces activation of the hypoxia signaling cascade, irrespective of viral infection.

Free Research Field

感染病理学

Academic Significance and Societal Importance of the Research Achievements

cell-to-cell 感染がウイルス感染で重要な役割を果たしていることはよく知られているが、そのメカニズムについてはよくわかっていない。本研究の実験結果から接着細胞とB細胞を共培養することにより普遍的にHypoxiaシグナル伝達系に刺激が入る可能性が示唆された。接着細胞とB細胞との接触によるHypoxiaシグナル伝達系の活性化がウイルスのcell-to-cell感染に利用されている可能性があり、新たな感染様式の解明につながることが期待される。