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Chandramouli S, Malito E, Nguyen T, et al. Structural basis for potent antibody-mediated neutralization of human cytomegalovirus. Sci Immunol. 2017;2(12)doi: 10.1126/sciimmunol.aan1457.
Chandramouli, S., Malito, E., Nguyen, T., Luisi, K., Donnarumma, D., Xing, Y., Norais, N., Yu, D., & Carfi, A. (2017). Structural basis for potent antibody-mediated neutralization of human cytomegalovirus. Science immunology, 2(12), . https://doi.org/10.1126/sciimmunol.aan1457
Chandramouli, Sumana, et al. "Structural basis for potent antibody-mediated neutralization of human cytomegalovirus." Science immunology vol. 2,12 (2017). doi: https://doi.org/10.1126/sciimmunol.aan1457
Chandramouli S, Malito E, Nguyen T, Luisi K, Donnarumma D, Xing Y, Norais N, Yu D, Carfi A. Structural basis for potent antibody-mediated neutralization of human cytomegalovirus. Sci Immunol. 2017 Jun 30;2(12). doi: 10.1126/sciimmunol.aan1457. PMID: 28783665.
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Sci Immunol. 2017 Jun 30;2(12). doi: 10.1126/sciimmunol.aan1457.

Structural basis for potent antibody-mediated neutralization of human cytomegalovirus.

Science immunology

Sumana Chandramouli, Enrico Malito, TuongVi Nguyen, Kate Luisi, Danilo Donnarumma, Yi Xing, Nathalie Norais, Dong Yu, Andrea Carfi

Affiliations

  1. GSK Vaccines, 14200 Shady Grove Road, Rockville, MD 20850, USA.
  2. GSK Vaccines, Via Fiorentina 1, 53100 Siena, Italy.
  3. GSK Vaccines, 14200 Shady Grove Road, Rockville, MD 20850, USA. [email protected].

PMID: 28783665 DOI: 10.1126/sciimmunol.aan1457

Abstract

Human cytomegalovirus (HCMV) is the leading viral cause of birth defects and organ transplant rejection. The HCMV gH/gL/UL128/UL130/UL131A complex (Pentamer) is the main target of humoral responses and thus a key vaccine candidate. We report two structures of Pentamer bound to human neutralizing antibodies, 8I21 and 9I6, at 3.0 and 5.9 Å resolution, respectively. The HCMV gH/gL architecture is similar to that of Epstein-Barr virus (EBV) except for amino-terminal extensions on both subunits. The extension of gL forms a subdomain composed of a three-helix bundle and a β hairpin that acts as a docking site for UL128/UL130/UL131A. Structural analysis reveals that Pentamer is a flexible molecule, and suggests sites for engineering stabilizing mutations. We also identify immunogenic surfaces important for cellular interactions by epitope mapping and functional assays. These results can guide the development of effective vaccines and immunotherapeutics against HCMV.

Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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