Functional screening for anti-CMV biologics identifies a broadly neutralizing epitope of an essential envelope protein
In: Nature Communications Nature Communications, Jg. 7 (2016), Heft 1, S. 1-15
Online
unknown
Zugriff:
The prototypic β-herpesvirus human cytomegalovirus (CMV) establishes life-long persistence within its human host. The CMV envelope consists of various protein complexes that enable wide viral tropism. More specifically, the glycoprotein complex gH/gL/gO (gH-trimer) is required for infection of all cell types, while the gH/gL/UL128/130/131a (gH-pentamer) complex imparts specificity in infecting epithelial, endothelial and myeloid cells. Here we utilize state-of-the-art robotics and a high-throughput neutralization assay to screen and identify monoclonal antibodies (mAbs) targeting the gH glycoproteins that display broad-spectrum properties to inhibit virus infection and dissemination. Subsequent biochemical characterization reveals that the mAbs bind to gH-trimer and gH-pentamer complexes and identify the antibodies' epitope as an ‘antigenic hot spot' critical for virus entry. The mAbs inhibit CMV infection at a post-attachment step by interacting with a highly conserved central alpha helix-rich domain. The platform described here provides the framework for development of effective CMV biologics and vaccine design strategies.
Human cytomegalovirus (CMV) poses a risk for immunosuppressed patients and newborns, with limited treatment options available. Here, Gardner et al. use a high-throughput approach and identify monoclonal antibodies that bind a highly conserved domain in the viral glycoprotein gH as potent inhibitors of CMV infection.
Titel: |
Functional screening for anti-CMV biologics identifies a broadly neutralizing epitope of an essential envelope protein
|
---|---|
Autor/in / Beteiligte Person: | Schwarz, Toni M. ; Gardner, Thomas J. ; Moran, Thomas M. ; Stein, Kathryn R. ; Kraus, Thomas ; Noriega, Vanessa M. ; J. Andrew Duty ; Tortorella, Domenico |
Link: | |
Zeitschrift: | Nature Communications Nature Communications, Jg. 7 (2016), Heft 1, S. 1-15 |
Veröffentlichung: | Nature Publishing Group, 2016 |
Medientyp: | unknown |
ISSN: | 2041-1723 (print) |
Schlagwort: |
|
Sonstiges: |
|