FHL1はチクングニャウイルス感染の主な宿主因子です

Laurent Meertens¹, Mohamed Lamine Hafirassou², Thérèse Couderc³

¹INSERM U944, CNRS UMR 7212, Genomes & Cell Biology of Disease Unit, Institut de Recherche Saint-Louis, Université de Paris, Hôpital Saint-Louis, Paris, France. laurent.meertens@inserm.fr.

Nature

|September 27, 2019

まとめ

四半のLIMドメインタンパク質1 (FHL1) はチクンギュンヤウイルス (CHIKV) 感染に不可欠です. FHL1を阻害することでCHIKVを抑制し,蚊媒介の病気に対する新たな治療標的となる.

科学分野:

ウイルス学
分子生物学
免疫学

背景:

チクングンヤウイルス (CHIKV) は,重発したアルファウイルスで,筋肉骨や関節の痛みを引き起こします.
CHIKV感染に重要な宿主因子の理解は,効果的な治療法の開発に不可欠です.

研究の目的:

CHIKVの許容性や病原性にとって不可欠なヒト細胞因子を特定する.
CHIKV感染における四半 LIM ドメインタンパク質1 (FHL1) の役割を調査する.

主な方法:

ヒトとマウスの細胞のFHL1発現を抑制する遺伝子サイレンス
様々なアルファウイルスとフラビウイルスによる感染検査
FHL1とCHIKV nsP3のタンパク質相互作用に関する研究
FHL1欠乏細胞とFhl1ノックアウトマウスにおけるCHIKV感染の分析

主要な成果:

FHL1の消去はCHIKVとオニョンニョンウイルスによる感染を抑制したが,他のアルファウイルスやフラビウイルスによる感染は抑制しなかった.
FHL1の発現は,通常抵抗性のある細胞におけるCHIKV感染を促した.
FHL1はCHIKV nsP3と直接相互作用し,ウイルスのRNA複製に不可欠である.
CHIKV感染は,Fhl1- ノックアウトマウスと,FHL1- 欠乏した患者由来細胞では検出されなかった.

結論:

FHL1はCHIKV感染と病原性を可能にする重要な宿主因子です.
CHIKV nsP3とFHL1の相互作用は,抗CHIKV治療の開発の有望なターゲットです.

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