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Nat Commun. 2016 Dec 14;7:13627. doi: 10.1038/ncomms13627.

Functional screening for anti-CMV biologics identifies a broadly neutralizing epitope of an essential envelope protein.

Author information

1
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
2
Center for Therapeutic Antibody Development, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.

Abstract

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.

PMID:
27966523
PMCID:
PMC5171902
DOI:
10.1038/ncomms13627
[Indexed for MEDLINE]
Free PMC Article

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