+Search query
-Structure paper
Title | Single-cell analysis of memory B cells from top neutralizers reveals multiple sites of vulnerability within HCMV Trimer and Pentamer. |
---|---|
Journal, issue, pages | Immunity, Vol. 56, Issue 11, Page 2602-2620.e10, Year 2023 |
Publish date | Nov 14, 2023 |
Authors | Matthias Zehner / Mira Alt / Artem Ashurov / Jory A Goldsmith / Rebecca Spies / Nina Weiler / Justin Lerma / Lutz Gieselmann / Dagmar Stöhr / Henning Gruell / Eric P Schultz / Christoph Kreer / Linda Schlachter / Hanna Janicki / Kerstin Laib Sampaio / Cora Stegmann / Michelle D Nemetchek / Sabrina Dähling / Leon Ullrich / Ulf Dittmer / Oliver Witzke / Manuel Koch / Brent J Ryckman / Ramin Lotfi / Jason S McLellan / Adalbert Krawczyk / Christian Sinzger / Florian Klein / |
PubMed Abstract | Human cytomegalovirus (HCMV) can cause severe diseases in fetuses, newborns, and immunocompromised individuals. Currently, no vaccines are approved, and treatment options are limited. Here, we ...Human cytomegalovirus (HCMV) can cause severe diseases in fetuses, newborns, and immunocompromised individuals. Currently, no vaccines are approved, and treatment options are limited. Here, we analyzed the human B cell response of four HCMV top neutralizers from a cohort of 9,000 individuals. By single-cell analyses of memory B cells targeting the pentameric and trimeric HCMV surface complexes, we identified vulnerable sites on the shared gH/gL subunits as well as complex-specific subunits UL and gO. Using high-resolution cryogenic electron microscopy, we revealed the structural basis of the neutralization mechanisms of antibodies targeting various binding sites. Moreover, we identified highly potent antibodies that neutralized a broad spectrum of HCMV strains, including primary clinical isolates, that outperform known antibodies used in clinical trials. Our study provides a deep understanding of the mechanisms of HCMV neutralization and identifies promising antibody candidates to prevent and treat HCMV infection. |
External links | Immunity / PubMed:37967532 |
Methods | EM (single particle) |
Resolution | 2.8 - 3.4 Å |
Structure data | EMDB-41156, PDB-8tco: EMDB-41157: Global reconstruction for HCMV Trimer in complex with CS2it1p2_F7K Fab and CS4tt1p1_E3K Fab EMDB-41158: CS2it1p2_F7K local refinement for HCMV Trimer in complex with CS2it1p2_F7K Fab and CS4tt1p1_E3K Fab EMDB-41160: CS4tt1p1_E3K local refinement for HCMV Trimer in complex with CS2it1p2_F7K Fab and CS4tt1p1_E3K Fab EMDB-41161: gH base local refinement for HCMV Trimer in complex with CS2it1p2_F7K Fab and CS4tt1p1_E3K Fab EMDB-41179, PDB-8tea: EMDB-41180: Global reconstruction for HCMV Pentamer in complex with CS2pt1p2_A10L Fab and CS3pt1p4_C1L Fab |
Chemicals | ChemComp-NAG: |
Source |
|
Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / Virus / glycoprotein / antibody / VIRAL PROTEIN-IMMUNE SYSTEM complex / VIRAL PROTEIN |