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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\u2019 epitope as an \u2018antigenic hot spot\u2019 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.<\/jats:p>","DOI":"10.1038\/ncomms13627","type":"journal-article","created":{"date-parts":[[2016,12,14]],"date-time":"2016-12-14T10:18:46Z","timestamp":1481710726000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Functional screening for anti-CMV biologics identifies a broadly neutralizing epitope of an essential envelope protein"],"prefix":"10.1038","volume":"7","author":[{"given":"Thomas J.","family":"Gardner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn R.","family":"Stein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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