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-Structure paper
Title | Structural basis for antibody-mediated neutralization of lymphocytic choriomeningitis virus. |
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Journal, issue, pages | Cell Chem Biol, Vol. 30, Issue 4, Page 403-411.e4, Year 2023 |
Publish date | Apr 20, 2023 |
Authors | Alex Moon-Walker / Zeli Zhang / Dawid S Zyla / Tierra K Buck / Haoyang Li / Ruben Diaz Avalos / Sharon L Schendel / Kathryn M Hastie / Shane Crotty / Erica Ollmann Saphire / |
PubMed Abstract | The mammarenavirus lymphocytic choriomeningitis virus (LCMV) is a globally distributed zoonotic pathogen that can be lethal in immunocompromised patients and can cause severe birth defects if ...The mammarenavirus lymphocytic choriomeningitis virus (LCMV) is a globally distributed zoonotic pathogen that can be lethal in immunocompromised patients and can cause severe birth defects if acquired during pregnancy. The structure of the trimeric surface glycoprotein, essential for entry, vaccine design, and antibody neutralization, remains unknown. Here, we present the cryoelectron microscopy (cryo-EM) structure of the LCMV surface glycoprotein (GP) in its trimeric pre-fusion assembly both alone and in complex with a rationally engineered monoclonal neutralizing antibody termed 18.5C-M28 (M28). Additionally, we show that passive administration of M28, either as a prophylactic or therapeutic, protects mice from LCMV clone 13 (LCMV) challenge. Our study illuminates not only the overall structural organization of LCMV GP and the mechanism for its inhibition by M28 but also presents a promising therapeutic candidate to prevent severe or fatal disease in individuals who are at risk of infection by a virus that poses a threat worldwide. |
External links | Cell Chem Biol / PubMed:36990092 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.19 - 3.26 Å |
Structure data | EMDB-27538, PDB-8dmh: EMDB-27539, PDB-8dmi: |
Chemicals | ChemComp-NAG: |
Source |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / Viral glycoprotein / arenavirus / LCMV / GP / antibody / neutralization / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex |