Elucidation of the molecular basis for HIV-1 vif/tat mRNA production by analyzing adaptive mutations and relevant sequence database

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07042
• 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: The University of Tokushima
• Principal Investigator: NOMAGUCHI Masako 徳島大学, 大学院医歯薬学研究部(医学域), 教授 (80452647)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: HIV-1 / cis-acting element / スプライシング / 遺伝子発現 / ウイルス複製 / 変異・適応 / 同義置換

Outline of Final Research Achievements

HIV-1 is a representative virus with high mutation and adaptation abilities. Understanding the HIV-1 adaptation process leads to the establishment of effective strategies to control viral replication. We have identified various synonymous mutations that affect HIV-1 replication ability based on the HIV-1 sequence database analysis. In this study, we newly found that five synonymous single-nucleotide mutations around the splicing acceptor 3 (SA3) site reduce HIV-1 replication ability. Worthy of note, one of the five mutations suppressed multi-cycle HIV-1 replication without affecting infectivity and virion production in single-cycle assay systems. This result suggests that there may be a novel regulatory region on the HIV-1 genome and an unknown restriction machinery in host cells. Elucidation of the molecular basis underlying the inhibition of HIV-1 replication by the single-nucleotide mutation around the SA3 site is underway in our laboratory.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

HIV-1のようなRNAウイルスは、複製に必須の複数のcis-acting elementをゲノム上に有している。本研究で実施した塩基配列ベースでの変異・適応の解析は、HIV-1の高い変異・適応能の制御戦略構築や新たなcis-acting elementの同定に繋がり得る。上述のSA3周辺で見出したマルチサイクルの複製能を低下させる1塩基置換の同定は、HIV-1ゲノム上の新規の複製調節領域、および、宿主細胞内での未知のHIV-1複製制御機構の存在を示唆している。本研究の推進により、HIV-1複製とその制御に関して新たな知見を提供することを目指す。