Characterization of a discontinuous neutralizing epitope on glycoprotein B of human cytomegalovirus
Spindler N, Ruecker P, Pötzsch S, Diestel U, Sticht H, Martin-Parras L, Winkler T, Mach M (2013)
Publication Type: Journal article
Publication year: 2013
Journal
Publisher: American Society for Microbiology
Book Volume: 87
Pages Range: 8927-39
Journal Issue: 16
DOI: 10.1128/JVI.00434-13
Abstract
Human cytomegalovirus (HCMV) is a ubiquitously distributed pathogen that causes severe disease in immunosuppressed patients and newborn infants infected in utero. The viral envelope glycoprotein B (gB) is an attractive molecule for active vaccination and passive immunoprophylaxis and therapy. Using human monoclonal antibodies (MAbs), we have recently identified antigenic region 4 (AD-4) on gB as an important target for neutralizing antibodies. AD-4 is formed by a discontinuous sequence comprising amino acids 121 to 132 and 344 to 438 of gB of HCMV strain AD169. To map epitopes for human antibodies on this protein domain, we used a three-dimensional (3D) model of HCMV gB to identify surface-exposed amino acids on AD-4 and selected juxtaposed residues for alanine scans. A tyrosine (Y) at position 364 and a lysine (K) at position 379 (the YK epitope), which are immediate neighbors on the AD-4 surface, were found to be essential for binding of the human MAbs. Recognition of AD-4 by sera from HCMV-infected individuals also was largely dependent on these two residues, indicating a general importance for the antibody response against AD-4. A panel of AD-4 recombinant viruses harboring mutations at the crucial antibody binding sites was generated. The viruses showed significantly reduced susceptibility to neutralization by AD-4-specific MAbs or polyclonal AD-4-specific antibodies, indicating that the YK epitope is dominant for the AD-4-specific neutralizing antibody response during infection. To our knowledge, this is the first molecular identification of a functional discontinuous epitope on HCMV gB. Induction of antibodies specific for this epitope may be a desirable goal following vaccination with gB.
Authors with CRIS profile
Nadja Spindler
Medizinische Fakultät
Sonja Pötzsch
Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene
Uschi Diestel
Lehrstuhl für Biotechnik (Proteinstruktur und -design)
Heinrich Sticht
Professur für Bioinformatik
Thomas Winkler
Professur für Genetik
Michael Mach
Medizinische Fakultät
Involved external institutions
Switzerland (CH)How to cite
APA:
Spindler, N., Ruecker, P., Pötzsch, S., Diestel, U., Sticht, H., Martin-Parras, L.,... Mach, M. (2013). Characterization of a discontinuous neutralizing epitope on glycoprotein B of human cytomegalovirus. Journal of Virology, 87(16), 8927-39. https://doi.org/10.1128/JVI.00434-13
MLA:
Spindler, Nadja, et al. "Characterization of a discontinuous neutralizing epitope on glycoprotein B of human cytomegalovirus." Journal of Virology 87.16 (2013): 8927-39.
BibTeX: Download