| 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
The Gn subcomponent of the Gn-Gc assembly that envelopes the human and animal pathogen, Rift Valley fever virus (RVFV), is a primary target of the neutralizing antibody response. To better understand the molecular basis for immune recognition, we raised a class of neutralizing monoclonal antibodies (nAbs) against RVFV Gn, which exhibited protective efficacy in a mouse infection model. Structural characterization revealed that these nAbs were directed to the membrane-distal domain of RVFV Gn and likely prevented virus entry into a host cell by blocking fusogenic rearrangements of the Gn-Gc lattice. Genome sequence analysis confirmed that this region of the RVFV Gn-Gc assembly was under selective pressure and constituted a site of vulnerability on the virion surface. These data provide a blueprint for the rational design of immunotherapeutics and vaccines capable of preventing RVFV infection and a model for understanding Ab-mediated neutralization of bunyaviruses more generally.
A Protective Monoclonal Antibody Targets a Site of Vulnerability on the Surface of Rift Valley Fever Virus.,Allen ER, Krumm SA, Raghwani J, Halldorsson S, Elliott A, Graham VA, Koudriakova E, Harlos K, Wright D, Warimwe GM, Brennan B, Huiskonen JT, Dowall SD, Elliott RM, Pybus OG, Burton DR, Hewson R, Doores KJ, Bowden TA Cell Rep. 2018 Dec 26;25(13):3750-3758.e4. doi: 10.1016/j.celrep.2018.12.001. PMID:30590046[12]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Allen ER, Krumm SA, Raghwani J, Halldorsson S, Elliott A, Graham VA, Koudriakova E, Harlos K, Wright D, Warimwe GM, Brennan B, Huiskonen JT, Dowall SD, Elliott RM, Pybus OG, Burton DR, Hewson R, Doores KJ, Bowden TA. A Protective Monoclonal Antibody Targets a Site of Vulnerability on the Surface of Rift Valley Fever Virus. Cell Rep. 2018 Dec 26;25(13):3750-3758.e4. doi: 10.1016/j.celrep.2018.12.001. PMID:30590046 doi:http://dx.doi.org/10.1016/j.celrep.2018.12.001
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