Evaluation methods for viral gene NS1 regulating cytokine storm induced with influenza virus

2015 Fiscal Year Final Research Report

• Project/Area Number: 24659268
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Laboratory medicine
• Research Institution: Teikyo University
• Principal Investigator: Suzuki Kazuo 帝京大学, 医療共通教育研究センター, 教授 (20192130)
• Co-Investigator(Kenkyū-buntansha): KATO Yusuke 徳島大学, 疾患酵素学研究センター, 准教授 (70596816)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: インフルエンザ / A/H5N1 / 高病原性 / 分子構造 / ARDS / 肺上皮細胞 / タイトジャンクション

Outline of Final Research Achievements

Avian influenza H5N1 has shown high mortality rate in human with 60%. Non-structural protein 1 (NS1) is a virulence factor of H5N1. Mutation at the 42nd residue within the RNA-binding domain (RBD) of NS1 dramatically changes the degree of pathogenicity of H5N1 in mice. We here studied the impact of this mutation on the function of RBD, and found that RBD with S42 binds double-stranded RNA (dsRNA), whereas that with P42 does not. Analysis of structural models of the RBD proteins with S42 and P42 suggested remarkable difference in the structure of the dsRNA-binding interface, whereas structural analysis did not indicate difference between those RBD proteins. Our results suggest that the single amino acid replacement induces a minor, but global structural change leading to the loss of function of NS1 thereby the change in the degree of pathogenicity In addition, PL site of NS1 may associate with down-regulation of tight junction molecules on epithelial cells in lung.

Free Research Field

感染症と免疫