6iek
Structure of RVFV Gn and human monoclonal antibody R12
Structural highlights
FunctionGP_RVFV Structural component of the virion that interacts with glycoprotein C (By similarity). It shields the hydrophobic fusion loops of the glycoprotein C, preventing premature fusion (By similarity). The glycoprotein protrusions are arranged on an icosahedral lattice, with T=12 triangulation (PubMed:19193794, PubMed:23319635). 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 (By similarity). Plays a role in the packaging of ribonucleoproteins and polymerase during virus assembly (By similarity).[UniProtKB:P09613][UniProtKB:P21401][1] [2] Structural component of the virion that interacts with glycoprotein N (By similarity). Acts as a class II fusion protein that is activated upon acidification and subsequent repositioning of the glycoprotein N (PubMed:23319635, PubMed:29097548). The glycoprotein protrusions are arranged on an icosahedral lattice, with T=12 triangulation (PubMed:19193794, PubMed:23319635). 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 (By similarity).[UniProtKB:P09613][3] [4] [5] Plays a role for virus dissemination in the mosquito.[UniProtKB:P21401][6] Plays a role for virus dissemination in mosquitoes.[UniProtKB:P21401] Publication Abstract from PubMedRift Valley fever virus (RVFV) is a mosquito-borne pathogen that causes substantial morbidity and mortality in livestock and humans. To date, there are no licensed human vaccines or therapeutics available. Here, we report the isolation of monoclonal antibodies from a convalescent patient, targeting the RVFV envelope proteins Gn and Gc. The Gn-specific monoclonal antibodies exhibited much higher neutralizing activities in vitro and protection efficacies in mice against RVFV infection, compared to the Gc-specific monoclonal antibodies. The Gn monoclonal antibodies were found to interfere with soluble Gn binding to cells and prevent infection by blocking the attachment of virions to host cells. Structural analysis of Gn complexed with four Gn-specific monoclonal antibodies resulted in the definition of three antigenic patches (A, B and C) on Gn domain I. Both patches A and B are major neutralizing epitopes. Our results highlight the potential of antibody-based therapeutics and provide a structure-based rationale for designing vaccines against RVFV. Neutralization mechanism of human monoclonal antibodies against Rift Valley fever virus.,Wang Q, Ma T, Wu Y, Chen Z, Zeng H, Tong Z, Gao F, Qi J, Zhao Z, Chai Y, Yang H, Wong G, Bi Y, Wu L, Shi R, Yang M, Song J, Jiang H, An Z, Wang J, Yilma TD, Shi Y, Liu WJ, Liang M, Qin C, Gao GF, Yan J Nat Microbiol. 2019 Apr 1. pii: 10.1038/s41564-019-0411-z. doi:, 10.1038/s41564-019-0411-z. PMID:30936489[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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