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

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; Poehlmann, Stefan; Muench, Jan; Fackler, Oliver T.; Kirchhoff, Frank and Sauter, Daniel (2019): Guanylate-Binding Proteins 2 and 5 Exert Broad Antiviral Activity by Inhibiting Furin-Mediated Processing of Viral Envelope Proteins. In: Cell Reports, Vol. 27, No. 7

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 GB 2/5 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.

• Item Type: Journal article
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 2211-1247
• Language: English