| Structural highlights
Function
GP_RVFVZ Structural component of the virion that interacts with glycoprotein C (PubMed:18715915). It shields the hydrophobic fusion loops of the glycoprotein C, preventing premature fusion (PubMed:29367607). The glycoprotein protrusions are arranged on an icosahedral lattice, with T=12 triangulation (PubMed:18715915, PubMed:29367607). They are able to attach the virion to the host cell receptor CD209/DC-SIGN and to promote fusion of membranes with the late endosome after endocytosis of the virion (PubMed:21767814). Plays a role in the packaging of ribonucleoproteins and polymerase during virus assembly (PubMed:21445316).[1] [2] [3] [4] Structural component of the virion that interacts with glycoprotein N (PubMed:18715915). Acts as a class II fusion protein that is activated upon acidification and subsequent repositioning of the glycoprotein N (PubMed:29367607). The glycoprotein protrusions are arranged on an icosahedral lattice, with T=12 triangulation (PubMed:18715915, PubMed:29367607). They are able to attach the virion to the host cell receptor CD209/DC-SIGN and to promote fusion of membranes with the late endosome after endocytosis of the virion (PubMed:21767814).[5] [6] [7] Plays a role in the inhibition of virus-induced apoptosis. Plays a role for virus dissemination in vertebrates.[8] [9] Plays a role for virus dissemination in mosquitoes. May act as a structural virion protein in insects.[10] [11]
Publication Abstract from PubMed
Entry of enveloped viruses relies on insertion of hydrophobic residues of the viral fusion protein into the host cell membrane. However, the intermediate conformations during fusion remain unknown. Here, we address the fusion mechanism of Rift Valley fever virus. We determine the crystal structure of the Gn glycoprotein and fit it with the Gc fusion protein into cryo-electron microscopy reconstructions of the virion. Our analysis reveals how the Gn shields the hydrophobic fusion loops of the Gc, preventing premature fusion. Electron cryotomography of virions interacting with membranes under acidic conditions reveals how the fusogenic Gc is activated upon removal of the Gn shield. Repositioning of the Gn allows extension of Gc and insertion of fusion loops in the outer leaflet of the target membrane. These data show early structural transitions that enveloped viruses undergo during host cell entry and indicate that analogous shielding mechanisms are utilized across diverse virus families.
Shielding and activation of a viral membrane fusion protein.,Halldorsson S, Li S, Li M, Harlos K, Bowden TA, Huiskonen JT Nat Commun. 2018 Jan 24;9(1):349. doi: 10.1038/s41467-017-02789-2. PMID:29367607[12]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Freiberg AN, Sherman MB, Morais MC, Holbrook MR, Watowich SJ. Three-dimensional organization of Rift Valley fever virus revealed by cryoelectron tomography. J Virol. 2008 Nov;82(21):10341-8. PMID:18715915 doi:10.1128/JVI.01191-08
- ↑ Piper ME, Sorenson DR, Gerrard SR. Efficient cellular release of Rift Valley fever virus requires genomic RNA. PLoS One. 2011 Mar 21;6(3):e18070. PMID:21445316 doi:10.1371/journal.pone.0018070
- ↑ Lozach PY, Kühbacher A, Meier R, Mancini R, Bitto D, Bouloy M, Helenius A. DC-SIGN as a receptor for phleboviruses. Cell Host Microbe. 2011 Jul 21;10(1):75-88. PMID:21767814 doi:10.1016/j.chom.2011.06.007
- ↑ Halldorsson S, Li S, Li M, Harlos K, Bowden TA, Huiskonen JT. Shielding and activation of a viral membrane fusion protein. Nat Commun. 2018 Jan 24;9(1):349. doi: 10.1038/s41467-017-02789-2. PMID:29367607 doi:http://dx.doi.org/10.1038/s41467-017-02789-2
- ↑ Freiberg AN, Sherman MB, Morais MC, Holbrook MR, Watowich SJ. Three-dimensional organization of Rift Valley fever virus revealed by cryoelectron tomography. J Virol. 2008 Nov;82(21):10341-8. PMID:18715915 doi:10.1128/JVI.01191-08
- ↑ Lozach PY, Kühbacher A, Meier R, Mancini R, Bitto D, Bouloy M, Helenius A. DC-SIGN as a receptor for phleboviruses. Cell Host Microbe. 2011 Jul 21;10(1):75-88. PMID:21767814 doi:10.1016/j.chom.2011.06.007
- ↑ Halldorsson S, Li S, Li M, Harlos K, Bowden TA, Huiskonen JT. Shielding and activation of a viral membrane fusion protein. Nat Commun. 2018 Jan 24;9(1):349. doi: 10.1038/s41467-017-02789-2. PMID:29367607 doi:http://dx.doi.org/10.1038/s41467-017-02789-2
- ↑ Terasaki K, Won S, Makino S. The C-terminal region of Rift Valley fever virus NSm protein targets the protein to the mitochondrial outer membrane and exerts antiapoptotic function. J Virol. 2013 Jan;87(1):676-82. PMID:23097454 doi:10.1128/JVI.02192-12
- ↑ Kreher F, Tamietti C, Gommet C, Guillemot L, Ermonval M, Failloux AB, Panthier JJ, Bouloy M, Flamand M. The Rift Valley fever accessory proteins NSm and P78/NSm-GN are distinct determinants of virus propagation in vertebrate and invertebrate hosts. Emerg Microbes Infect. 2014 Oct;3(10):e71. PMID:26038497 doi:10.1038/emi.2014.71
- ↑ Weingartl HM, Zhang S, Marszal P, McGreevy A, Burton L, Wilson WC. Rift Valley fever virus incorporates the 78 kDa glycoprotein into virions matured in mosquito C6/36 cells. PLoS One. 2014 Jan 28;9(1):e87385. PMID:24489907 doi:10.1371/journal.pone.0087385
- ↑ Kreher F, Tamietti C, Gommet C, Guillemot L, Ermonval M, Failloux AB, Panthier JJ, Bouloy M, Flamand M. The Rift Valley fever accessory proteins NSm and P78/NSm-GN are distinct determinants of virus propagation in vertebrate and invertebrate hosts. Emerg Microbes Infect. 2014 Oct;3(10):e71. PMID:26038497 doi:10.1038/emi.2014.71
- ↑ Halldorsson S, Li S, Li M, Harlos K, Bowden TA, Huiskonen JT. Shielding and activation of a viral membrane fusion protein. Nat Commun. 2018 Jan 24;9(1):349. doi: 10.1038/s41467-017-02789-2. PMID:29367607 doi:http://dx.doi.org/10.1038/s41467-017-02789-2
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