Regulation of structure-function network of EV-A71 capsid protein by VP1-145 substitution

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16330
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54030:Infectious disease medicine-related
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Kotani Osamu 国立感染症研究所, 病原体ゲノム解析研究センター, 室長 (00769581)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: エンテロウイルス / カプシドタンパク質 / 構造ゆらぎ / 相互作用ネットワーク

Outline of Final Research Achievements

The capsid protein of EV-A71 constitutes the virion surface, playing pivotal roles in viral life cycle and virus-host interactions. Previous studies have shown that a single amino acid substitution at position 145 in VP1 (VP1-145) coincidentally alters a variety of viral biological phenotypes. However, the structural mechanism underlying the VP1-145 mediated co-regulation of viral phenotypes remain unclear. To address this issue, we examined the effects of VP1-145 on the physical properties of the capsid model. The MD results showed that the VP1-145 is the allosteric regulator to coincidentally modulate physical properties of multiple interaction surfaces of the capsid. On the other hand, Neutralization studies showed that mutations altered the neutralization sensitivity of a group of specific antibodies. This would be a structural basis for the VP1-145 mediated co-regulation of interaction network between virus and host factor.

Free Research Field

感染症の構造生物学

Academic Significance and Societal Importance of the Research Achievements

EV-A71 カプシドタンパク質VP1-145の変異がウイルスの多種にわたる性質変化をどのようにして制御しているかは不明な点が多かった。本研究で構築したEV-A71カプシド構造解析基盤は、未だ謎の多いEV-A71の構造活性制御機構の解明に貢献する。さらには、EV-A71感染の重症化機構の解明、変異を勘案したEV-A71感染制御法開発など、基礎・開発研究の双方の新展開に貢献すると期待される。