A Quantitative Genetic Interaction Map of HIV Infection.

CD4-Positive T-Lymphocytes / immunology Epistasis, Genetic HIV Infections / genetics HIV-1 / genetics Host-Pathogen Interactions / genetics Humans Immunity, Innate / genetics Interferon Regulatory Factor-7 / genetics Interferons / genetics Mutation Signal Transduction / genetics Transcription Factors / genetics
CCR4-NOT CNOT complex IRF7 combinatorial genetics epistasis map host-pathogen network biology innate immunity interferon stimulated gene vE-MAP viral infection genetic screen

Journal

Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571

Informations de publication

Date de publication:
16 04 2020
Historique:
received: 23 08 2019
revised: 10 01 2020
accepted: 02 02 2020
pubmed: 23 2 2020
medline: 14 8 2020
entrez: 22 2 2020
Statut: ppublish

Résumé

We have developed a platform for quantitative genetic interaction mapping using viral infectivity as a functional readout and constructed a viral host-dependency epistasis map (vE-MAP) of 356 human genes linked to HIV function, comprising >63,000 pairwise genetic perturbations. The vE-MAP provides an expansive view of the genetic dependencies underlying HIV infection and can be used to identify drug targets and study viral mutations. We found that the RNA deadenylase complex, CNOT, is a central player in the vE-MAP and show that knockout of CNOT1, 10, and 11 suppressed HIV infection in primary T cells by upregulating innate immunity pathways. This phenotype was rescued by deletion of IRF7, a transcription factor regulating interferon-stimulated genes, revealing a previously unrecognized host signaling pathway involved in HIV infection. The vE-MAP represents a generic platform that can be used to study the global effects of how different pathogens hijack and rewire the host during infection.

Identifiants

DOI: 10.1016/j.molcel.2020.02.004 PMID: 32084337 PMC: PMC7462049
pubmed: 32084337
pii: S1097-2765(20)30074-5
doi: 10.1016/j.molcel.2020.02.004
pmc: PMC7462049
mid: NIHMS1568844
pii:
doi:

Substances chimiques

CNOT1 protein, human 0
IRF7 protein, human 0
Interferon Regulatory Factor-7 0
Transcription Factors 0
Interferons 9008-11-1

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

197-209.e7

Subventions

Organisme : NIGMS NIH HHS
ID : F32 GM108303
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI135990
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR028962
Pays : United States
Organisme : NIGMS NIH HHS
ID : P50 GM082250
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI027763
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI135972
Pays : United States
Organisme : NIAID NIH HHS
ID : P50 AI150476
Pays : United States
Organisme : NIH HHS
ID : S10 OD018522
Pays : United States
Organisme : NIH HHS
ID : S10 OD026880
Pays : United States

Informations de copyright

Copyright © 2020 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests The Krogan Laboratory has received research support from Vir Biotechnology and F. Hoffmann-La Roche. A.M. is a co-founder of Spotlight Therapeutics and Arsenal Therapeutics. A.M. serves on the scientific advisory board of PACT Pharma, is an advisor to Sonoma Biotherapeutics, and was a former advisor to Juno Therapeutics. The Marson laboratory has received sponsored research support from Juno Therapeutics, Epinomics, Sanofi, and a gift from Gilead.

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Auteurs

David E Gordon (DE)

Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA; Gladstone Institutes, San Francisco, CA 94158, USA.

Ariane Watson (A)

School of Biomolecular and Biomedical Science and Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland; Systems Biology Ireland, University College Dublin, Belfield, Dublin 4, Ireland.

Assen Roguev (A)

Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA.

Simin Zheng (S)

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Gwendolyn M Jang (GM)

Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA.

Joshua Kane (J)

Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA.

Jiewei Xu (J)

Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA.

Jeffrey Z Guo (JZ)

Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA.

Erica Stevenson (E)

Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA; Gladstone Institutes, San Francisco, CA 94158, USA.

Danielle L Swaney (DL)

Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA; Gladstone Institutes, San Francisco, CA 94158, USA.

Kathy Franks-Skiba (K)

Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA.

Erik Verschueren (E)

Genentech, South San Francisco, CA 94080, USA.

Michael Shales (M)

Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA.

David C Crosby (DC)

Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA.

Alan D Frankel (AD)

Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA.

Alexander Marson (A)

Gladstone Institutes, San Francisco, CA 94158, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.

Ivan Marazzi (I)

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Gerard Cagney (G)

School of Biomolecular and Biomedical Science and Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland; Systems Biology Ireland, University College Dublin, Belfield, Dublin 4, Ireland.

Nevan J Krogan (NJ)

Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA; Gladstone Institutes, San Francisco, CA 94158, USA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: nevan.krogan@ucsf.edu.

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Classifications MeSH

questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Lymphocytes T CD4+ › A Quantitative Genetic Interaction Map of HIV...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épistasie › A Quantitative Genetic Interaction Map of HIV...
questionsmedicales.fr › Maladies du système immunitaire › Déficits immunitaires › Infections à VIH › A Quantitative Genetic Interaction Map of HIV...
questionsmedicales.fr › Virus › Virus à ARN › Retroviridae › Lentivirus › Lentivirus des primates › VIH (Virus de l'Immunodéficience Humaine) › VIH-1 (Virus de l'Immunodéficience Humaine de type 1) › A Quantitative Genetic Interaction Map of HIV...
questionsmedicales.fr › Phénomènes biologiques › Interactions hôte-microbes › Interactions hôte-pathogène › A Quantitative Genetic Interaction Map of HIV...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › A Quantitative Genetic Interaction Map of HIV...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunité › Immunité innée › A Quantitative Genetic Interaction Map of HIV...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de régulation d'interféron › Facteur-7 de régulation d'interféron › A Quantitative Genetic Interaction Map of HIV...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interférons › A Quantitative Genetic Interaction Map of HIV...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › A Quantitative Genetic Interaction Map of HIV...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › A Quantitative Genetic Interaction Map of HIV...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › A Quantitative Genetic Interaction Map of HIV...