A comprehensive Drosophila resource to identify key functional interactions between SARS-CoV-2 factors and host proteins.

Humans Animals SARS-CoV-2 / genetics COVID-19 Drosophila Actins Animals, Genetically Modified
ATE1 CP: Microbiology DRC Drosophila Drosophila Covid-19 resource NSP8 NSPs Orf3a SARS-CoV-2 arginylation human interactors non-structural proteins

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
29 08 2023
Historique:
received: 21 02 2023
revised: 18 05 2023
accepted: 05 07 2023
medline: 4 9 2023
pubmed: 22 7 2023
entrez: 22 7 2023
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.celrep.2023.112842 PMID: 37480566
pubmed: 37480566
pii: S2211-1247(23)00853-7
doi: 10.1016/j.celrep.2023.112842
pii:
doi:

Substances chimiques

Actins 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

112842

Subventions

Organisme : NIH HHS
ID : R24 OD028242
Pays : United States
Organisme : NIH HHS
ID : R24 OD022005
Pays : United States
Organisme : NIH HHS
ID : R24 OD031447
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM117321
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM144608
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI162911
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD083092
Pays : United States
Organisme : NINDS NIH HHS
ID : P30 NS047101
Pays : United States

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests E.B. has equity interests in Synbal Inc., a company that may potentially benefit from the research results. E.B. also serves on the Board of Directors and Scientific Advisory Board of Synbal. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict-of-interest policies.

Auteurs

Annabel Guichard (A)

Section of Cell and Developmental Biology, University of California, San Diego (UCSD), La Jolla, CA 92093, USA.

Shenzhao Lu (S)

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 (O)

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 (D)

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 (Y)

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 (M)

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 (S)

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 (JC)

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 (KL)

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 (M)

Section of Cell and Developmental Biology, University of California, San Diego (UCSD), La Jolla, CA 92093, USA.

Ruth Schwartz (R)

Section of Cell and Developmental Biology, University of California, San Diego (UCSD), La Jolla, CA 92093, USA.

Mei-Chu Huang (MC)

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 (D)

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 (H)

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 (L)

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 (WW)

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 (A)

Section of Cell and Developmental Biology, University of California, San Diego (UCSD), La Jolla, CA 92093, USA.

Pranjali Bhagwat (P)

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 (S)

Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.

Kenneth H Wan (KH)

Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.

Takashi Ohsako (T)

Advanced Technology Center, Kyoto Institute of Technology, Kyoto 606-8585, Japan.

Toshiyuki Takano-Shimizu (T)

Kyoto Drosophila Stock Center and Faculty of Applied Biology, Kyoto Institute of Technology, Kyoto 616-8354, Japan.

Susan E Celniker (SE)

Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.

Michael F Wangler (MF)

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 (S)

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. Electronic address: yamamoto@bcm.edu.

Hugo J Bellen (HJ)

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. Electronic address: hbellen@bcm.edu.

Ethan Bier (E)

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. Electronic address: ebier@ucsd.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › A comprehensive Drosophila resource to...
questionsmedicales.fr › Eucaryotes › Animaux › A comprehensive Drosophila resource to...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN à brin positif › Nidovirales › Coronaviridae › Coronavirus › Betacoronavirus › Virus du SRAS › SARS-CoV-2 › A comprehensive Drosophila resource to...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Pneumopathie infectieuse › Pneumopathie virale › COVID-19 › A comprehensive Drosophila resource to...
questionsmedicales.fr › Eucaryotes › Animaux › Invertébrés › Arthropodes › Insectes › Pterygota › Neoptera › Holometabola › Diptera › Drosophilidae › Drosophila › A comprehensive Drosophila resource to...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du cytosquelette › Protéines des microfilaments › Actines › A comprehensive Drosophila resource to...
questionsmedicales.fr › Stades d'organismes › Organismes génétiquement modifiés › Animal génétiquement modifié › A comprehensive Drosophila resource to...