Analysis of respiratory virus activation mechanism by bacterial proteases

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04596
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Veterinary medical science
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: SAKAI KOUJI 国立感染症研究所, ウイルス第三部, 主任研究官 (70515535)
• Co-Investigator(Kenkyū-buntansha): 小川 道永 国立感染症研究所, 細菌第一部, 室長 (80361624)
• Research Collaborator: NAKAJIMA Katsuhiro ; KITAZAWA Minori ; Nathanan Sangsriratnakul ; KOMURA Miyuki
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 細菌性プロテアーゼ / インフルエンザAウイルス / 膜蛋白質 / 開裂 / 重症化肺炎

Outline of Final Research Achievements

The host protease TMPRSS2 plays an essential role in HA proteolytic activation of the influenza A virus (IAV) for the pathogenic expression of primary viral pneumonia. Secondary infectious pneumonia involving bacterial infection, accounts for the majority of IAV deaths, but the detailed mechanism is unknown. We preformed to verify using mouse model. However promotion of HA cleavage of IAV by bacterial protease was not observed. On the other hand, after passages in TMPRSS2 knockout mice, an H3N2 and H7N1 subtype IAVs began to undergo cleavage activation of HA, showing high virulence in the mice due to the loss of an oligosaccharide in the HA stalk region. Thus, these TMPRSS2 knockout mice adapted IAVs acquired cleavability by an alternative HA activation proteases.

Free Research Field

獣医学