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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 c...

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Hauptverfasser: Braun, Elisabeth (VerfasserIn) , Hotter, Dominik (VerfasserIn) , Wombacher, Rebecka (VerfasserIn) , Fackler, Oliver Till (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 14 May 2019
In: Cell reports
Year: 2019, Jahrgang: 27, Heft: 7, Pages: 2092-2104
ISSN:2211-1247
DOI:10.1016/j.celrep.2019.04.063
Online-Zugang:Verlag, Volltext: https://doi.org/10.1016/j.celrep.2019.04.063
Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S2211124719305364
Volltext
Verfasserangaben: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, and Daniel Sauter
Beschreibung
Zusammenfassung: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.
Beschreibung:Elisabeth Braun and Dominik Hotter contributed equally
The article ends with page 2104.e10
Gesehen am 05.07.2019
Beschreibung:Online Resource
ISSN:2211-1247
DOI:10.1016/j.celrep.2019.04.063

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