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Review
. 2020 Jun 24;12(6):682.
doi: 10.3390/v12060682.

Role of the Guanine Nucleotide Exchange Factor GBF1 in the Replication of RNA Viruses

José L Martínez  1 , Carlos F Arias  1
Affiliations
Review

Role of the Guanine Nucleotide Exchange Factor GBF1 in the Replication of RNA Viruses

José L Martínez et al. Viruses. .

Abstract

The guanine nucleotide exchange factor GBF1 is a well-known factor that can activate different ADP-ribosylation factor (Arf) proteins during the regulation of different cellular vesicular transport processes. In the last decade, it has become increasingly evident that GBF1 can also regulate different steps of the replication cycle of RNA viruses belonging to different virus families. GBF1 has been shown not only to facilitate the intracellular traffic of different viral and cellular elements during infection, but also to modulate the replication of viral RNA, the formation and maturation of viral replication complexes, and the processing of viral proteins through mechanisms that do not depend on its canonical role in intracellular transport. Here, we review the various roles that GBF1 plays during the replication of different RNA viruses.

Keywords: GBF1; RNA viruses; vesicle transport.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Schematic diagram of the roles of COPI, COPII, and clathrin in the vesicular secretory pathway. ER, endoplasmic reticulum; ERGIC, ER-Golgi intermediate compartment.
Figure 2
Figure 2
Mechanism of COPI transport. COPI vesicle formation starts when the small GTPase Arf1, bound to GDP (Arf1-GDP), associates with the Golgi-specific Brefeldin A (BFA) resistance factor 1 (GBF1), a guanine nucleotide exchange factor (GEF) that catalyzes the activation of Arf1 by promoting the exchange of GDP for a GTP molecule (step 1). This exchange induces a conformational change in Arf1 that leads to the exposure of a myristoyl group that allows the association of this protein with the membrane [31] (step 2). The membrane-bound Arf1-GTP then promotes the recruitment of the preformed COPI coat formed by seven subunits, called α, β, β’, δ, ε, γ and ζ, and the Arf-GTPase-activating protein 1 (ArfGAP1) (step 3). The formation of the Arf1-GTP-COPI-ArfGAP1 complex in the membranes stimulates the binding and concentration of different cargoes (step 4) and induces the bending of the membrane into a vesicle (step 5). Once the vesicle is completed, it buds from the membrane with a coat of COPI (step 6). Finally, the coat proteins are disassembled when the GTPase activity of Arf1 is enhanced by ArfGAP1, leading to the hydrolysis of the GTP molecule, promoting the release of Arf1-GDP, the COPI subunits, and ArfGAP1 from the vesicle to produce the free carrier vesicle used in the vesicular transport (step 7) [32,33].
Figure 3
Figure 3
Domain organization of GBF1. The positions of the Sec7, DCB, HUS, and HDS1-3 domains are indicated. The amino acid residues comprised in each domain are shown in parentheses.
See this image and copyright information in PMC

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