Cell Fusion Induced by a Fusion-Active Form of Human Cytomegalovirus Glycoprotein B (gB) Is Inhibited by Antibodies Directed at Antigenic Domain 5 in the Ectodomain of gB

Author:

Reuter Nina1,Kropff Barbara1,Schneiderbanger Julia Karin1,Alt Mira2,Krawczyk Adalbert23,Sinzger Christian4,Winkler Thomas H.5,Britt William J.6,Mach Michael1,Thomas Marco1ORCID

Affiliation:

1. Virologisches Institut, Klinische und Molekulare Virologie, Friedrich Alexander Universität Erlangen-Nürnberg, Erlangen, Germany

2. Institut für Virologie, Universitätsklinikum Duisburg-Essen, Essen, Germany

3. Klinik für Infektiologie, Medizinisches Forschungszentrum, Universitätsklinikum Duisburg-Essen, Essen, Germany

4. Institut für Virologie, Universitätsklinikum Ulm, Ulm, Germany

5. Nikolaus-Fiebiger-Zentrum für Molekulare Medizin, Friedrich Alexander Universität Erlangen-Nürnberg, Erlangen, Germany

6. Departments of Pediatrics, Microbiology and Neurobiology, Children's Hospital of Alabama, University of Alabama School of Medicine, Birmingham, Alabama, USA

Abstract

HCMV is a major global health concern, and antiviral chemotherapy remains problematic due to toxicity of available compounds and the emergence of drug-resistant viruses. Thus, an HCMV vaccine represents a priority for both governmental and pharmaceutical research programs. A major obstacle for the development of a vaccine is a lack of knowledge of the nature and specificities of protective immune responses that should be induced by such a vaccine. Glycoprotein B of HCMV is an important target for neutralizing antibodies and, hence, is often included as a component of intervention strategies. By generation of fusion-active gB chimeras, we were able to identify target structures of neutralizing antibodies that potently block gB-induced membrane fusion. This experimental system provides an approach to screen for antibodies that interfere with gB’s fusogenic activity. In summary, our data will likely contribute to both rational vaccine design and the development of antibody-based therapies against HCMV.

Funder

Else Kröner-Fresenius-Stiftung

HHS | NIH | OSC | Common Fund

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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