Elucidation of our recent findings on the protective role of prion protein against lethal infection with influenza A viruses is useful for development of a new type of anti-influenza drugs

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K15380
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Infectious disease medicine
• Research Institution: The University of Tokushima
• Principal Investigator: SAKAGUCHI Suehiro 徳島大学, 先端酵素学研究所(次世代), 教授 (60274635)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: プリオン蛋白質 / インフルエンザ / インフルエンザウイルス / 活性酸素種 / 銅イオン / 銅/亜鉛依存性スーパーオキシドジスムターゼ / ノックアウトマウス / アポトーシス

Outline of Final Research Achievements

Here we show that the cellular prion protein, PrPC, is expressed in lung epithelial cells. Compared with wild-type (WT) mice, PrPC-null mice (Prnp0/0) developed higher mortality after infection with influenza A viruses (IAVs). Infected Prnp0/0 lungs were severely injured, with higher apoptosis of the epithelial cells, and contained higher ROS than control WT lungs. Treatment with a ROS scavenger rescued Prnp0/0 mice from the lethal infection with IAV. These results indicate that PrPC provides a protection against lethal infection with IAVs by reducing ROS in infected lungs. Cu contents and the activity of anti-oxidant enzyme Cu/Zn-dependent superoxide dismutase, SOD1, were lower in Prnp0/0 lungs than in WT lungs. It is thus conceivable that PrPC functions to maintain Cu contents and regulate SOD1 in lungs, thereby reducing ROS in IAV-infected lungs and eventually protecting from lethal infection with IAVs, suggesting that PrPC might be a new target for anti-influenza therapeutics.

Free Research Field

分子生物学