Guanylate-Binding Proteins 2 and 5 Exert Broad Antiviral Activity by Inhibiting Furin-Mediated Processing of Viral Envelope Proteins
Summary: 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 ce...
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Elsevier
2019-05-01
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Series: | Cell Reports |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719305364 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Elisabeth Braun Dominik Hotter Lennart Koepke Fabian Zech Rüdiger Groß Konstantin M.J. Sparrer Janis A. Müller Christian K. Pfaller Elena Heusinger Rebecka Wombacher Kathrin Sutter Ulf Dittmer Michael Winkler Graham Simmons Martin R. Jakobsen Karl-Klaus Conzelmann Stefan Pöhlmann Jan Münch Oliver T. Fackler Frank Kirchhoff Daniel Sauter |
spellingShingle |
Elisabeth Braun Dominik Hotter Lennart Koepke Fabian Zech Rüdiger Groß Konstantin M.J. Sparrer Janis A. Müller Christian K. Pfaller Elena Heusinger Rebecka Wombacher Kathrin Sutter Ulf Dittmer Michael Winkler Graham Simmons Martin R. Jakobsen Karl-Klaus Conzelmann Stefan Pöhlmann Jan Münch Oliver T. Fackler Frank Kirchhoff Daniel Sauter Guanylate-Binding Proteins 2 and 5 Exert Broad Antiviral Activity by Inhibiting Furin-Mediated Processing of Viral Envelope Proteins Cell Reports |
author_facet |
Elisabeth Braun Dominik Hotter Lennart Koepke Fabian Zech Rüdiger Groß Konstantin M.J. Sparrer Janis A. Müller Christian K. Pfaller Elena Heusinger Rebecka Wombacher Kathrin Sutter Ulf Dittmer Michael Winkler Graham Simmons Martin R. Jakobsen Karl-Klaus Conzelmann Stefan Pöhlmann Jan Münch Oliver T. Fackler Frank Kirchhoff Daniel Sauter |
author_sort |
Elisabeth Braun |
title |
Guanylate-Binding Proteins 2 and 5 Exert Broad Antiviral Activity by Inhibiting Furin-Mediated Processing of Viral Envelope Proteins |
title_short |
Guanylate-Binding Proteins 2 and 5 Exert Broad Antiviral Activity by Inhibiting Furin-Mediated Processing of Viral Envelope Proteins |
title_full |
Guanylate-Binding Proteins 2 and 5 Exert Broad Antiviral Activity by Inhibiting Furin-Mediated Processing of Viral Envelope Proteins |
title_fullStr |
Guanylate-Binding Proteins 2 and 5 Exert Broad Antiviral Activity by Inhibiting Furin-Mediated Processing of Viral Envelope Proteins |
title_full_unstemmed |
Guanylate-Binding Proteins 2 and 5 Exert Broad Antiviral Activity by Inhibiting Furin-Mediated Processing of Viral Envelope Proteins |
title_sort |
guanylate-binding proteins 2 and 5 exert broad antiviral activity by inhibiting furin-mediated processing of viral envelope proteins |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2019-05-01 |
description |
Summary: 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. : The cellular protease furin processes numerous substrates, including the envelope proteins of many viral pathogens. Here, Braun et al. show that guanylate-binding proteins 2 and 5 are interferon-inducible restriction factors that reduce virion infectivity by inhibiting furin activity and consequently maturation of viral envelope glycoproteins. Keywords: GBPs, restriction factor, furin, HIV, influenza A virus, measles virus, Zika virus, viral envelope proteins |
url |
http://www.sciencedirect.com/science/article/pii/S2211124719305364 |
work_keys_str_mv |
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doaj-23fcf6a2dd424c5193317bfaa8ba1f2e2020-11-25T00:39:44ZengElsevierCell Reports2211-12472019-05-0127720922104.e10Guanylate-Binding Proteins 2 and 5 Exert Broad Antiviral Activity by Inhibiting Furin-Mediated Processing of Viral Envelope ProteinsElisabeth Braun0Dominik Hotter1Lennart Koepke2Fabian Zech3Rüdiger Groß4Konstantin M.J. Sparrer5Janis A. Müller6Christian K. Pfaller7Elena Heusinger8Rebecka Wombacher9Kathrin Sutter10Ulf Dittmer11Michael Winkler12Graham Simmons13Martin R. Jakobsen14Karl-Klaus Conzelmann15Stefan Pöhlmann16Jan Münch17Oliver T. Fackler18Frank Kirchhoff19Daniel Sauter20Institute of Molecular Virology, Ulm University Medical Center, Ulm 89081, GermanyInstitute of Molecular Virology, Ulm University Medical Center, Ulm 89081, GermanyInstitute of Molecular Virology, Ulm University Medical Center, Ulm 89081, GermanyInstitute of Molecular Virology, Ulm University Medical Center, Ulm 89081, GermanyInstitute of Molecular Virology, Ulm University Medical Center, Ulm 89081, GermanyInstitute of Molecular Virology, Ulm University Medical Center, Ulm 89081, GermanyInstitute of Molecular Virology, Ulm University Medical Center, Ulm 89081, GermanyPaul-Ehrlich-Institute, Langen 63225, GermanyInstitute of Molecular Virology, Ulm University Medical Center, Ulm 89081, GermanyCenter for Integrative Infectious Disease Research, Integrative Virology, University Hospital Heidelberg, Heidelberg 69120, GermanyInstitute for Virology, University Clinics Essen, University of Duisburg-Essen, Essen 45147, GermanyInstitute for Virology, University Clinics Essen, University of Duisburg-Essen, Essen 45147, GermanyInfection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen 37077, GermanyBlood Systems Research Institute, Department of Pathology and Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94118, USADepartment of Biomedicine, Aarhus University, Aarhus 8000, DenmarkMax von Pettenkofer Institute Virology, Medical Faculty, and Gene Center, Ludwig-Maximilians-University Munich, Munich 81377, GermanyInfection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen 37077, Germany; Faculty of Biology and Psychology, University Göttingen, Göttingen 37073, GermanyInstitute of Molecular Virology, Ulm University Medical Center, Ulm 89081, GermanyCenter for Integrative Infectious Disease Research, Integrative Virology, University Hospital Heidelberg, Heidelberg 69120, Germany; German Center for Infection Research (DZIF), Partner Site Heidelberg, Heidelberg 69120, GermanyInstitute of Molecular Virology, Ulm University Medical Center, Ulm 89081, GermanyInstitute of Molecular Virology, Ulm University Medical Center, Ulm 89081, Germany; Corresponding authorSummary: 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. : The cellular protease furin processes numerous substrates, including the envelope proteins of many viral pathogens. Here, Braun et al. show that guanylate-binding proteins 2 and 5 are interferon-inducible restriction factors that reduce virion infectivity by inhibiting furin activity and consequently maturation of viral envelope glycoproteins. Keywords: GBPs, restriction factor, furin, HIV, influenza A virus, measles virus, Zika virus, viral envelope proteinshttp://www.sciencedirect.com/science/article/pii/S2211124719305364 |