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Guanylate-Binding proteins 2 and 5 exert broad antiviral activity by inhibiting Furin-Mediated processing of viral envelope proteins

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Erstveröffentlichung
2019-05-14
DOI
10.18725/OPARU-32230
Wissenschaftlicher Artikel


Authors
Braun, Elisabeth
Hotter, Dominik
Koepke, Lennart
Zech, Fabian
Groß, Rüdiger
et al.
Institutions
UKU. Institut für Molekulare Virologie
External cooperations
Paul-Ehrlich-Institut
Universitätsklinikum Heidelberg
Universität Duisburg-Essen
Deutsches Primatenzentrum - Leibnitz-Institut für Primatenforschung
University of California
et al.
Published in
Cell Reports ; 27 (2019), 7. - S. 2092-2104. - ISSN 2211-1247
Link to original publication
https://dx.doi.org/10.1016/j.celrep.2019.04.063
Peer review
ja
Document version
publishedVersion
License
CC BY-NC-ND 4.0
Abstract
Guanylate-binding protein (GBP) 5 is an interferon (IFN)-inducible cellular factor reducing HIV-1 infectivity by an incompletely understood mechanism. Here, we show that this activity is shared by GBP2, but not by other members of the human GBP family. GBP2/5 decrease the activity of the cellular proprotein convertase furin, which mediates conversion of the HIV-1 envelope protein (Env) precursor gp160 into mature gp120 and gp41. Because this process primes HIV-1 Env for membrane fusion, viral particles produced in the presence of GBP2/5 are poorly infectious due to increased incorporation of non-functional gp160. Furin activity is critical for the processing of envelope glycoproteins of many viral pathogens. Consistently, GBP2/5 also inhibit Zika, measles, and influenza A virus replication and decrease infectivity of viral particles carrying glycoproteins of Marburg and murine leukemia viruses. Collectively, our results show that GPB2/5 exert broad antiviral activity by suppressing the activity of the virus-dependency factor furin.
Funding information
Bausteinprogramm der Medizinischen Fakultät / Universität Ulm
SFB 1279 / Nutzung des menschlichen Peptidoms für die Entwicklung neuer antimikrobieller und anti-Krebs Therapeutika / DFG / SFB / 316249678
SPP 1923 / Innate Sensing and Restriction of Retroviruses / DFG
TRR 83 / Molekulare Architektur und zelluläre Funktionen von Lipid/Protein Komplexen / DFG [TRR237]
SFB 548 / Analyse und Modulation allergischer und autoimmunologischer Krankheiten / DFG [Ki548/16]
etc.
EU Project
VIAR / Virus-induced autophagy restriction / EC / H2020 / 794803
Is supplemented by
https://www.sciencedirect.com/science/article/pii/S2211124719305364?via%3Dihub#app2
Subject Headings
HIV [GND]
Angeborene Immunität [GND]
HIV [MeSH]
Immunity, Innate [MeSH]
Keywords
GBP
Dewey Decimal Group
DDC 610 / Medicine & health

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Citation example

Braun, Elisabeth et al. (2020): Guanylate-Binding proteins 2 and 5 exert broad antiviral activity by inhibiting Furin-Mediated processing of viral envelope proteins. Open Access Repositorium der Universität Ulm. http://dx.doi.org/10.18725/OPARU-32230

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