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


ABSTRACT: The prototypic ?-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.

SUBMITTER: Gardner TJ 

PROVIDER: S-EPMC5171902 | biostudies-other | 2016 Dec

REPOSITORIES: biostudies-other

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

Gardner Thomas J TJ   Stein Kathryn R KR   Duty J Andrew JA   Schwarz Toni M TM   Noriega Vanessa M VM   Kraus Thomas T   Moran Thomas M TM   Tortorella Domenico D  

Nature communications 20161214


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-through  ...[more]

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