Identification of novel receptor in the sialic acid-independent infection of H5N1 highly pathogenic avian influenza virus

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K10043
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: KAJIWARA Naoki 公益財団法人東京都医学総合研究所, 疾患制御研究分野, 主任研究員 (70453917)
• Co-Investigator(Kenkyū-buntansha): 芝崎 太 公益財団法人東京都医学総合研究所, 病院等連携研究センター, 研究員 (90300954) ; 大保木 啓介 公益財団法人東京都医学総合研究所, 病院等連携研究センター, 副参事研究員 (80415108)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: インフルエンザ / H5N1 / 感染 / シアル酸 / ヘマグルチニン

Outline of Final Research Achievements

H5N1 highly pathogenic avian influenza virus has multiple basic amino acids at cleavage site of hemagglutinin. This unique motif showed the cell-penetrating activity against various cells and lung tissues. In this study, we found the candidate genes of a novel receptor such as coagulation factor II thrombin receptor (F2R), frizzled class receptor (FZD), and sphingosine-1-phosphate receptor 1 (S1PR1) using DNA microarray and haploid genetic screening. The candidate gene-overexpressed cells were prepared and validation experiments were carried out, but no functional enhancement was observed. On the other hand, the cell-penetrating activity was impaired in a mutant CHO cell line (pgsA745) that lacks xylosyltransferase activity. These findings suggest that proteoglycans may be involved in sialic acid-independent infection of H5N1 highly pathogenic avian influenza virus.

Free Research Field

感染症学

Academic Significance and Societal Importance of the Research Achievements

本研究は、H5N1高病原性鳥インフルエンザウイルスのシアル酸非依存的な感染経路における受容体の同定を通じて、ウイルスの感染性の理解を深める点で学術的に非常に大きな意味を持つ。また、H5N1高病原性鳥インフルエンザウイルスの感染を予防、治療しうる分子的根拠を明らかにすることが可能であり、治療薬開発を通じて医療に貢献するばかりでなく、感染対策を講ずることにより社会的混乱や経済的損失の防止にもつながることが期待される。