8TEA

HCMV Pentamer in complex with CS2pt1p2_A10L Fab and CS3pt1p4_C1L Fab

Summary for 8TEA

• Entry DOI: 10.2210/pdb8tea/pdb
• EMDB information: 41179
• Descriptor: Envelope protein UL128, Envelope glycoprotein UL130, UL131A, ... (7 entities in total)
• Functional Keywords: virus, glycoprotein, antibody, viral protein
• Biological source: Human betaherpesvirus 5; More
• Total number of polymer chains: 7
• Total formula weight: 153857.88

Authors

Goldsmith, J.A.,McLellan, J.S. (deposition date: 2023-07-05, release date: 2023-08-09, Last modification date: 2024-10-09)

Primary citation

Zehner, M.,Alt, M.,Ashurov, A.,Goldsmith, J.A.,Spies, R.,Weiler, N.,Lerma, J.,Gieselmann, L.,Stohr, D.,Gruell, H.,Schultz, E.P.,Kreer, C.,Schlachter, L.,Janicki, H.,Laib Sampaio, K.,Stegmann, C.,Nemetchek, M.D.,Dahling, S.,Ullrich, L.,Dittmer, U.,Witzke, O.,Koch, M.,Ryckman, B.J.,Lotfi, R.,McLellan, J.S.,Krawczyk, A.,Sinzger, C.,Klein, F.
Single-cell analysis of memory B cells from top neutralizers reveals multiple sites of vulnerability within HCMV Trimer and Pentamer.
Immunity, 56:2602-2620.e10, 2023

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 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.

PubMed: 37967532
DOI: 10.1016/j.immuni.2023.10.009

Experimental method

ELECTRON MICROSCOPY (3.4 Å)