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。
◆このリソースは、ショウジョウバエにSARS-CoV-2タンパク質と人間のタンパク質に相当する蝿株を含みます。研究では、特に9つのSARS-CoV-2タンパク質がショウジョウバエの成虫の翅に欠陥を引き起こすことがわかりました。また、SARS-CoV-2タンパク質の1つであるNSP8は他のNSPと連携し、特にヒトタンパク質のATE1と強く相互作用することも明らかになりました。
<関連情報>
- https://today.ucsd.edu/story/fly-toolkit-created-for-investigating-covid-19-infection-mechanisms
- https://www.cell.com/cell-reports/fulltext/S2211-1247(23)00853-7
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
DOI:https://doi.org/10.1016/j.celrep.2023.112842
Highlights
•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
Summary
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.
