Analysis of the functional regulation of HIV structural protein Gag

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07594
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49060:Virology-related
• Research Institution: Yokohama City University
• Principal Investigator: MIYAKAWA Kei 横浜市立大学, 医学部, 准教授 (20580046)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 宿主-ウイルス相互作用

Outline of Final Research Achievements

The type I interferon (IFN) response is a robust anti-viral response that induces the transcription of several IFN-stimulated genes (ISGs). However, the effects of ISGs, particularly on the HIV-1 Gag protein, remain largely unknown. In this study, we screened ISG-encoded proteins by bioluminescence resonance energy transfer to identify the host effectors that suppressed Gag function. Consequently, we identified the transmembrane protein MAL as a Gag-interacting ISG product. Expression of MAL substantially inhibited the production of HIV-1 particles, leading to the translocation, accumulation, and eventual lysosomal degradation of Gag in the host endosomal compartments. Notably, the antiviral activity of MAL was partially antagonized by the viral accessory protein Nef, as it interfered with the interaction between MAL and Gag. Therefore, this study reveals a previously unidentified antiviral function of MAL and its viral counteraction.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

本研究では、タンパク質間相互作用を生細胞でリアルタイムに検出可能な実験系を用いて、ヒト免疫不全ウイルスを顕著に抑制する機能をもつヒトタンパク質を多数同定し、宿主の自然免疫応答機構、およびウイルスがそれを克服する作用機序を明らかにした。これまで知られていなかったウイルスタンパク質の新たな機能が明らかとなり、ヒトが本来有する抗ウイルス活性を利用したHIV-1感染症の新規治療法開発に将来的に寄与するものと考えられる。