Guanylate-Binding Proteins 2 and 5 Exert Broad Antiviral Activity by Inhibiting Furin-Mediated Processing of Viral Envelope Proteins
2019 | journal article. A publication with affiliation to the University of Göttingen.
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Guanylate-Binding Proteins 2 and 5 Exert Broad Antiviral Activity by Inhibiting Furin-Mediated Processing of Viral Envelope Proteins
Braun, E.; Hotter, D.; Koepke, L.; Zech, F.; Groß, R.; Sparrer, K. M. & Müller, J. A. et al. (2019)
Cell Reports, 27(7) art. 2104.e10. DOI: https://doi.org/10.1016/j.celrep.2019.04.063
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Details
- Authors
- Braun, Elisabeth; Hotter, Dominik; Koepke, Lennart; Zech, Fabian; Groß, Rüdiger; Sparrer, Konstantin M.J.; Müller, Janis A.; Pfaller, Christian K.; Heusinger, Elena; Wombacher, Rebecka; Sutter, Kathrin; Dittmer, Ulf; Winkler, Michael; Simmons, Graham; Jakobsen, Martin R.; Conzelmann, Karl-Klaus; Pöhlmann, Stefan; Münch, Jan; Fackler, Oliver T.; Kirchhoff, Frank; Sauter, Daniel
- 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.
- Issue Date
- 2019
- Journal
- Cell Reports
- Language
- English