Cell Reports (Aug 2023)
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
Affiliations
- Annabel Guichard
- Section of Cell and Developmental Biology, University of California, San Diego (UCSD), La Jolla, CA 92093, USA
- Shenzhao Lu
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA
- Oguz Kanca
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA
- Daniel Bressan
- Section of Cell and Developmental Biology, University of California, San Diego (UCSD), La Jolla, CA 92093, USA; Instituto de Ciências Biomédicas (ICB), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro 21941-902, Brazil
- Yan Huang
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA
- Mengqi Ma
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA
- Sara Sanz Juste
- Section of Cell and Developmental Biology, University of California, San Diego (UCSD), La Jolla, CA 92093, USA; Department of Epigenetics & Molecular Carcinogenesis at MD Anderson, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; Center for Cancer Epigenetics, MD Anderson Cancer Center, Houston, TX, USA
- Jonathan C. Andrews
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA
- Kristy L. Jay
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA
- Marketta Sneider
- Section of Cell and Developmental Biology, University of California, San Diego (UCSD), La Jolla, CA 92093, USA
- Ruth Schwartz
- Section of Cell and Developmental Biology, University of California, San Diego (UCSD), La Jolla, CA 92093, USA
- Mei-Chu Huang
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA
- Danqing Bei
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA
- Hongling Pan
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA
- Liwen Ma
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA
- Wen-Wen Lin
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA
- Ankush Auradkar
- Section of Cell and Developmental Biology, University of California, San Diego (UCSD), La Jolla, CA 92093, USA
- Pranjali Bhagwat
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA
- Soo Park
- Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
- Kenneth H. Wan
- Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
- Takashi Ohsako
- Advanced Technology Center, Kyoto Institute of Technology, Kyoto 606-8585, Japan
- Toshiyuki Takano-Shimizu
- Kyoto Drosophila Stock Center and Faculty of Applied Biology, Kyoto Institute of Technology, Kyoto 616-8354, Japan
- Susan E. Celniker
- Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
- Michael F. Wangler
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA; Texas Children’s Hospital, Houston, TX 77030, USA
- Shinya Yamamoto
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Development, Disease Models & Therapeutics Graduate Program, Baylor College of Medicine, Houston, TX 77030, USA; Corresponding author
- Hugo J. Bellen
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Corresponding author
- Ethan Bier
- Section of Cell and Developmental Biology, University of California, San Diego (UCSD), La Jolla, CA 92093, USA; Tata Institute for Genetics and Society - UCSD, La Jolla, CA 92093, USA; Corresponding author
- Journal volume & issue
-
Vol. 42,
no. 8
p. 112842
Abstract
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.
