Investigation of novel mechanism(s) regarding HIV-1 capsid protein degradation and uncoating

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08435
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54030:Infectious disease medicine-related
• Research Institution: Kumamoto University
• Principal Investigator: Amano Masayuki 熊本大学, 病院, 特別研究員 (30575080)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: HIV-1 / キャプシド蛋白 / 蛋白自己崩壊 / 脱殻

Outline of Final Research Achievements

Capsid protein (CA), which is an essential structural protein for HIV-1 and forms a shell that encloses a viral RNA, maintains the shell structure with a certain strength in order to protect the viral RNA in the virion. On the other hand, in order to collapse CA shell smoothly and transport viral RNA to the nuclease (so-called “uncoating”) while new infection, it is also necessary for CA to have a certain degree of "instability". In this project, we newly discovered that 9 amino acids sequence (9AA) of CA C-terminal domain (CTD) is important factor for CA degradation, and that infectivity and replicative capacity are significantly impaired in HIV-1 variants containing CTD-9AA deleted CA.

Free Research Field

感染症内科

Academic Significance and Societal Importance of the Research Achievements

本研究ではHIV-1の必須構造蛋白であるキャプシド（CA）で認めるCA自己崩壊（自壊）の責任領域やその機序を検討し、更にHIV-1の脱殻・複製に対しCA自壊が及ぼす影響について評価するものであり、不明な点が多いHIV-1の細胞感染初期、特に脱殻時におけるCAの動態に関し、新たなコンセンサスの確立に貢献し得る可能性がある。更に得られた知見はCAを有する他のウイルスに関しても応用可能と考えられる。