Molecular Basis for Antibody-Mediated Neutralization of New World Hemorrhagic Fever Mammarenaviruses
Autor: | Selma Mahmutovic, Lars Clark, Jonathan Abraham, Ana M. Briggiler, Silvana Levis, Stephen C. Harrison, Delia Enria |
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Rok vydání: | 2015 |
Předmět: |
Cancer Research
Protein Conformation medicine.drug_class medicine.medical_treatment Passive immunity Antibodies Viral Crystallography X-Ray Monoclonal antibody Microbiology Article Epitope Immune system Virology Immunology and Microbiology(all) medicine Humans Molecular Biology Host cell surface Binding Sites Junin virus Membrane Glycoproteins biology biology.organism_classification Antibodies Neutralizing Hemorrhagic Fevers biology.protein Parasitology Antibody Protein Binding |
Zdroj: | Cell Host & Microbe. 18(6):705-713 |
ISSN: | 1931-3128 |
DOI: | 10.1016/j.chom.2015.11.005 |
Popis: | In the Western hemisphere, at least five mammarenaviruses cause human viral hemorrhagic fevers with high case fatality rates. Junín virus (JUNV) is the only hemorrhagic fever virus for which transfusion of survivor immune plasma that contains neutralizing antibodies (‘passive immunity’) is an established treatment. Here, we report the structure of the JUNV surface glycoprotein receptor-binding subunit (GP1) bound to a neutralizing monoclonal antibody. The antibody engages the GP1 site that binds transferrin receptor 1 (TfR1) – the host cell surface receptor for all New World hemorrhagic fever mammarenaviruses - and mimics an important receptor contact. We show that survivor immune plasma contains antibodies that bind the same epitope. We propose that viral receptor-binding site accessibility explains the success of passive immunity against JUNV and that this functionally conserved epitope is a potential target for therapeutics and vaccines to limit infection by all New World hemorrhagic fever mammarenaviruses. |
Databáze: | OpenAIRE |
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