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Structure of HCMV glycoprotein B in the postfusion conformation bound to a neutralizing human antibody

Author

Listed:
  • Sumana Chandramouli

    (GSK Vaccines)

  • Claudio Ciferri

    (GSK Vaccines
    Present address: Department of Structural Biology, Genentech Inc., 94080 South San Francisco, California, USA)

  • Pavel A. Nikitin

    (Novartis Institutes for Biomedical Research)

  • Stefano Caló

    (GSK Vaccines)

  • Rachel Gerrein

    (GSK Vaccines)

  • Kara Balabanis

    (GSK Vaccines)

  • James Monroe

    (GSK Vaccines)

  • Christy Hebner

    (Novartis Institutes for Biomedical Research)

  • Anders E. Lilja

    (GSK Vaccines
    Present address: Hookipa Biotech AG, 1030 Vienna, Austria)

  • Ethan C. Settembre

    (Novartis Influenza Vaccines)

  • Andrea Carfi

    (GSK Vaccines)

Abstract

Human cytomegalovirus (HCMV) poses a significant threat to immunocompromised individuals and neonates infected in utero. Glycoprotein B (gB), the herpesvirus fusion protein, is a target for neutralizing antibodies and a vaccine candidate due to its indispensable role in infection. Here we show the crystal structure of the HCMV gB ectodomain bound to the Fab fragment of 1G2, a neutralizing human monoclonal antibody isolated from a seropositive subject. The gB/1G2 interaction is dominated by aromatic residues in the 1G2 heavy chain CDR3 protruding into a hydrophobic cleft in the gB antigenic domain 5 (AD-5). Structural analysis and comparison with HSV gB suggest the location of additional neutralizing antibody binding sites on HCMV gB. Finally, immunoprecipitation experiments reveal that 1G2 can bind to HCMV virion gB suggesting that its epitope is exposed and accessible on the virus surface. Our data will support the development of vaccines and therapeutic antibodies against HCMV infection.

Suggested Citation

  • Sumana Chandramouli & Claudio Ciferri & Pavel A. Nikitin & Stefano Caló & Rachel Gerrein & Kara Balabanis & James Monroe & Christy Hebner & Anders E. Lilja & Ethan C. Settembre & Andrea Carfi, 2015. "Structure of HCMV glycoprotein B in the postfusion conformation bound to a neutralizing human antibody," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9176
    DOI: 10.1038/ncomms9176
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    Cited by:

    1. Momei Zhou & Benjamin Vollmer & Emily Machala & Muyuan Chen & Kay Grünewald & Ann M. Arvin & Wah Chiu & Stefan L. Oliver, 2023. "Targeted mutagenesis of the herpesvirus fusogen central helix captures transition states," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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