Guanylate-Binding Proteins 2 and 5 Exert Broad Antiviral Activity by Inhibiting Furin-Mediated Processing of Viral Envelope Proteins

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  • Elisabeth Braun, Institute of Molecular Virology, Ulm University Medical Center, Meyerhofstrasse 1, 89081, Ulm, Germany.
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  • Dominik Hotter, Institute of Molecular Virology, Ulm University Medical Center, Meyerhofstrasse 1, 89081, Ulm, Germany.
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  • Lennart Koepke, Institute of Molecular Virology, Ulm University Medical Center, Meyerhofstrasse 1, 89081, Ulm, Germany.
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  • Fabian Zech, Institute of Molecular Virology, Ulm University Medical Center, Meyerhofstrasse 1, 89081, Ulm, Germany.
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  • Rüdiger Groß, Institute of Molecular Virology, Ulm University Medical Center, Meyerhofstrasse 1, 89081, Ulm, Germany.
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  • Konstantin M J Sparrer, Institute of Molecular Virology, Ulm University Medical Center, Meyerhofstrasse 1, 89081, Ulm, Germany.
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  • Janis A Müller, Institute of Molecular Virology, Ulm University Medical Center, Meyerhofstrasse 1, 89081, Ulm, Germany.
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  • Christian K Pfaller, Paul-Ehrlich-Institute, Langen 63225, Germany.
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  • Elena Heusinger, Institute of Molecular Virology, Ulm University Medical Center, Meyerhofstrasse 1, 89081, Ulm, Germany.
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  • Rebecka Wombacher, Center for Integrative Infectious Disease Research, Integrative Virology, University Hospital Heidelberg, Heidelberg 69120, Germany.
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  • Kathrin Sutter, Institute for Virology, University Clinics Essen, University of Duisburg-Essen, Essen 45147, Germany.
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  • Ulf Dittmer, Institute for Virology, University Clinics Essen, University of Duisburg-Essen, Essen 45147, Germany.
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  • Michael Winkler, Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen 37077, Germany.
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  • Graham Simmons, Blood Systems Research Institute, Department of Pathology and Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94118, USA.
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  • Martin R Jakobsen
  • Karl-Klaus Conzelmann, Max von Pettenkofer Institute Virology, Medical Faculty, and Gene Center, Ludwig-Maximilians-University Munich, Munich 81377, Germany.
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  • Stefan Pöhlmann, Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen 37077, Germany; Faculty of Biology and Psychology, University Göttingen, Göttingen 37073, Germany.
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  • Jan Münch, Institute of Molecular Virology, Ulm University Medical Center, Meyerhofstrasse 1, 89081, Ulm, Germany.
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  • Oliver T Fackler, Center for Integrative Infectious Disease Research, Integrative Virology, University Hospital Heidelberg, Heidelberg 69120, Germany; German Center for Infection Research (DZIF), Partner Site Heidelberg, Heidelberg 69120, Germany.
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  • Frank Kirchhoff, Institute of Molecular Virology, Ulm University Medical Center, Meyerhofstrasse 1, 89081, Ulm, Germany.
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  • Daniel Sauter, Institute of Molecular Virology, Ulm University Medical Center, Ulm 89081, Germany. Electronic address: daniel.sauter@uni-ulm.de.

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.

OriginalsprogEngelsk
TidsskriftCell Reports
Vol/bind27
Nummer7
Sider (fra-til)2092-2104.e10
ISSN2211-1247
DOI
StatusUdgivet - 14 maj 2019
Eksternt udgivetJa

Bibliografisk note

Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

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