Language:

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

Journal of virology, 2020-08, Vol.94 (18) [Peer Reviewed Journal]

Copyright © 2020 American Society for Microbiology. ;Copyright © 2020 American Society for Microbiology. 2020 American Society for Microbiology ;ISSN: 0022-538X ;EISSN: 1098-5514 ;DOI: 10.1128/JVI.01276-20 ;PMID: 32641474

Full text available

Citations Cited by

Actions
1. Add to My Research
2. Remove from My Research
3. E-mail
4. Print
5. Permalink
6. Citation
7. EasyBib
8. EndNote
9. RefWorks
10. Delicious
11. Export RIS
12. Export BibTeX

Title:
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, Nina ; Kropff, Barbara ; Schneiderbanger, Julia Karin ; Alt, Mira ; Krawczyk, Adalbert ; Sinzger, Christian ; Winkler, Thomas H ; Britt, William J ; Mach, Michael ; Thomas, Marco
Sandri-Goldin, Rozanne M.
Subjects: Animals ; Antibodies, Monoclonal - metabolism ; Antibodies, Monoclonal - pharmacology ; Antibodies, Neutralizing - metabolism ; Antibodies, Neutralizing - pharmacology ; Antibodies, Viral - metabolism ; Antibodies, Viral - pharmacology ; Binding Sites ; Cell Fusion ; Cell Line ; Cytomegalovirus - drug effects ; Cytomegalovirus - genetics ; Cytomegalovirus - metabolism ; Epithelial Cells - drug effects ; Epithelial Cells - metabolism ; Epithelial Cells - virology ; Fibroblasts - drug effects ; Fibroblasts - metabolism ; Fibroblasts - virology ; Gene Expression ; Giant Cells - drug effects ; Giant Cells - metabolism ; Giant Cells - ultrastructure ; Giant Cells - virology ; HEK293 Cells ; Humans ; Mice ; Mutant Chimeric Proteins - chemistry ; Mutant Chimeric Proteins - genetics ; Mutant Chimeric Proteins - metabolism ; Primary Cell Culture ; Protein Binding ; Protein Conformation, alpha-Helical ; Protein Conformation, beta-Strand ; Protein Interaction Domains and Motifs ; Stromal Cells - drug effects ; Stromal Cells - metabolism ; Stromal Cells - virology ; Vaccines and Antiviral Agents ; Vesiculovirus - genetics ; Vesiculovirus - metabolism ; Viral Envelope Proteins - genetics ; Viral Envelope Proteins - metabolism
Is Part Of: Journal of virology, 2020-08, Vol.94 (18)
Description: Human cytomegalovirus (HCMV) is a ubiquitous pathogen that can cause severe clinical disease in allograft recipients and infants infected Virus-neutralizing antibodies defined have been proposed to confer protection against HCMV infection, and the virion envelope glycoprotein B (gB) serves as a major target of neutralizing antibodies. The viral fusion protein gB is nonfusogenic on its own and requires glycoproteins H (gH) and L (gL) for membrane fusion, which is in contrast to requirements of related class III fusion proteins, including vesicular stomatitis virus glycoprotein G (VSV-G) or baculovirus gp64. To explore requirements for gB's fusion activity, we generated a set of chimeras composed of gB and VSV-G or gp64, respectively. These gB chimeras were intrinsically fusion active and led to the formation of multinucleated cell syncytia when expressed in the absence of other viral proteins. Utilizing a panel of virus-neutralizing gB-specific monoclonal antibodies (MAbs), we could demonstrate that syncytium formation of the fusogenic gB/VSV-G chimera can be significantly inhibited by only a subset of neutralizing MAbs which target antigenic domain 5 (AD-5) of gB. This observation argues for differential modes of action of neutralizing anti-gB MAbs and suggests that blocking the membrane fusion function of gB could be one mechanism of antibody-mediated virus neutralization. In addition, our data have important implications for the further understanding of the conformation of gB that promotes membrane fusion as well as the identification of structures in AD-5 that could be targeted by antibodies to block this early step in HCMV infection. 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.
Publisher: United States: American Society for Microbiology
Language: English
Identifier: ISSN: 0022-538X
EISSN: 1098-5514
DOI: 10.1128/JVI.01276-20
PMID: 32641474
Source: MEDLINE
PubMed Central

Back to results list


INSPIRE LIBRARY - TON DUC THANG UNIVERSITY	(84-028) 37 755 057	Feedback
19 Nguyen Huu Tho St. Dist.7, HCM	thuvien@tdtu.edu.vn	Feedback

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

Copyright © 2020 American Society for Microbiology. ;Copyright © 2020 American Society for Microbiology. 2020 American Society for Microbiology ;ISSN: 0022-538X ;EISSN: 1098-5514 ;DOI: 10.1128/JVI.01276-20 ;PMID: 32641474

Searching Remote Databases, Please Wait