A Protective Monoclonal Antibody Targets a Site of Vulnerability on the Surface of Rift Valley Fever Virus
| العنوان: | A Protective Monoclonal Antibody Targets a Site of Vulnerability on the Surface of Rift Valley Fever Virus |
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| المؤلفون: | 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 |
| المصدر: | Cell Reports, Vol 25, Iss 13, Pp 3750-3758.e4 (2018) Cell Reports Allen, E R, Krumm, S A, Raghwani, J, Halldorsson, S, Elliott, A, Graham, V A, Koudriakova, E, Harlos, K, Wright, D, Warimwe, G M, Brennan, B, Huiskonen, J T, Dowall, S D, Elliott, R M, Pybus, O G, Burton, D R, Hewson, R, Doores, K J & Bowden, T A 2018, ' A Protective Monoclonal Antibody Targets a Site of Vulnerability on the Surface of Rift Valley Fever Virus ', Cell Reports, vol. 25, no. 13, pp. 3750-3758.e4 . https://doi.org/10.1016/j.celrep.2018.12.001 |
| بيانات النشر: | Elsevier, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | viruses, bunyavirus, Antibodies, Viral, Models, Biological, Article, immune response, Protein Domains, Viral Envelope Proteins, Neutralization Tests, antibody, vaccine, Chlorocebus aethiops, Animals, Humans, phlebovirus, structure, Amino Acid Sequence, Vero Cells, lcsh:QH301-705.5, virus-host interactions, Glycoproteins, Mice, Inbred BALB C, Antibodies, Monoclonal, neutralization, Rift Valley fever virus, antiviral, Antibodies, Neutralizing, Recombinant Proteins, HEK293 Cells, lcsh:Biology (General), Immunoglobulin G, Female, Immunization, Rabbits |
| الوصف: | Summary 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. Graphical Abstract Highlights • The Gn glycoprotein of Rift Valley fever virus elicits potent neutralizing antibodies • Derived a class of monoclonal antibodies that protects in an animal model • A distinct region on RVFV Gn constitutes a key site of vulnerability • Antibodies are predicted to prevent exposure of viral fusion loops Allen et al. reveal a molecular basis of antibody-mediated neutralization of Rift Valley fever virus, an important human and animal pathogen. They isolate and demonstrate the protective efficacy of a monoclonal antibody in a murine model of virus infection, providing a blueprint for rational therapeutic and vaccine design. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2211-1247 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::c65bee51bd01eeed6c6fccd71bc928d3 http://www.sciencedirect.com/science/article/pii/S2211124718319120 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.pmid.dedup....c65bee51bd01eeed6c6fccd71bc928d3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22111247 |
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