COVID-19感染メカニズムを調べるためのフライツールキットを作成(Fly Toolkit Created for Investigating COVID-19 Infection Mechanisms)


2023-07-21 カリフォルニア大学サンディエゴ校(UCSD)

◆そこで、複数の機関が共同でショウジョウバエを用いたツールキットを開発し、SARS-CoV-2遺伝子とヒトタンパク質の相互作用を評価するためのショートカットを提供するDrosophila COVIDリソース(DCR)を作成しました。


SARS-CoV-2因子と宿主タンパク質間の重要な機能的相互作用を同定するための包括的なショウジョウバエリソース A comprehensive Drosophila resource to identify key functional interactions between SARS-CoV-2 factors and host proteins

Annabel Guichard,Shenzhao Lu,Oguz Kanca,Daniel Bressan,Yan Huang,Mengqi Ma,Sara Sanz Juste,Jonathan C. Andrews,Kristy L. Jay,Marketta Sneider,Ruth Schwartz,Mei-Chu Huang,Danqing Bei,Hongling Pan,Liwen Ma,Wen-Wen Lin,Ankush Auradkar,Pranjali Bhagwat,Soo Park,Kenneth H. Wan,Takashi Ohsako,Toshiyuki Takano-Shimizu,Susan E. Celniker,Michael F. Wangler,Shinya Yamamoto,Hugo J. Bellen,Ethan Bier
Cell Reports  Published:July 20, 2023

COVID-19感染メカニズムを調べるためのフライツールキットを作成(Fly Toolkit Created for Investigating COVID-19 Infection Mechanisms)


•A Drosophila resource enables functional analysis of all SARS-Cov2 factors
This collection allows expression of viral factors and human binding partners
•It also includes GAL4 insertions mutating fly orthologs of host binding partners
•NSP8 interacts with other viral factors and with the ATE1 arginyltransferase


Development of effective therapies against SARS-CoV-2 infections relies on mechanistic knowledge of virus-host interface. Abundant physical interactions between viral and host proteins have been identified, but few have been functionally characterized. Harnessing the power of fly genetics, we develop a comprehensive Drosophila COVID-19 resource (DCR) consisting of publicly available strains for conditional tissue-specific expression of all SARS-CoV-2 encoded proteins, UAS-human cDNA transgenic lines encoding established host-viral interacting factors, and GAL4 insertion lines disrupting fly homologs of SARS-CoV-2 human interacting proteins. We demonstrate the utility of the DCR to functionally assess SARS-CoV-2 genes and candidate human binding partners. We show that NSP8 engages in strong genetic interactions with several human candidates, most prominently with the ATE1 arginyltransferase to induce actin arginylation and cytoskeletal disorganization, and that two ATE1 inhibitors can reverse NSP8 phenotypes. The DCR enables parallel global-scale functional analysis of SARS-CoV-2 components in a prime genetic model system.