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Cell Rep. 2019 May 14;27(7):2092-2104.e10. doi: 10.1016/j.celrep.2019.04.063.

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

Author information

1
Institute of Molecular Virology, Ulm University Medical Center, Ulm 89081, Germany.
2
Paul-Ehrlich-Institute, Langen 63225, Germany.
3
Center for Integrative Infectious Disease Research, Integrative Virology, University Hospital Heidelberg, Heidelberg 69120, Germany.
4
Institute for Virology, University Clinics Essen, University of Duisburg-Essen, Essen 45147, Germany.
5
Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen 37077, Germany.
6
Blood Systems Research Institute, Department of Pathology and Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94118, USA.
7
Department of Biomedicine, Aarhus University, Aarhus 8000, Denmark.
8
Max von Pettenkofer Institute Virology, Medical Faculty, and Gene Center, Ludwig-Maximilians-University Munich, Munich 81377, Germany.
9
Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen 37077, Germany; Faculty of Biology and Psychology, University Göttingen, Göttingen 37073, Germany.
10
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.
11
Institute of Molecular Virology, Ulm University Medical Center, Ulm 89081, Germany. Electronic address: daniel.sauter@uni-ulm.de.

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.

KEYWORDS:

GBPs; HIV; Zika virus; furin; influenza A virus; measles virus; restriction factor; viral envelope proteins

PMID:
31091448
DOI:
10.1016/j.celrep.2019.04.063
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