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Publication Abstract from PubMed

Cytomegalovirus (CMV) is a widespread opportunistic pathogen that causes birth defects when transmitted transplacentally and severe systemic illness in immunocompromised individuals. MSL-109, a human monoclonal IgG isolated from a CMV seropositive individual, binds to the essential CMV entry glycoprotein H (gH) and prevents infection of cells. Here, we suggest a mechanism for neutralization activity by MSL-109. We define a genetic basis for resistance to MSL-109 and have generated a structural model of gH that reveals the epitope of this neutralizing antibody. Using surface-based, time-resolved FRET, we demonstrate that gH/gL interacts with glycoprotein B (gB). Additionally, we detect homodimers of soluble gH/gL heterodimers and confirm this novel oligomeric assembly on full-length gH/gL expressed on the cell surface. We show that MSL-109 perturbs the dimerization of gH/gL:gH/gL, suggesting that dimerization of gH/gL may be required for infectivity. gH/gL homodimerization may be conserved between alpha- and betaherpesviruses, because both CMV and HSV gH/gL demonstrate self-association in the FRET system. This study provides evidence for a novel mechanism of action for MSL-109 and reveals a previously undescribed aspect of viral entry that may be susceptible to therapeutic intervention.

Mechanism for neutralizing activity by the anti-CMV gH/gL monoclonal antibody MSL-109.,Fouts AE, Comps-Agrar L, Stengel KF, Ellerman D, Schoeffler AJ, Warming S, Eaton DL, Feierbach B Proc Natl Acad Sci U S A. 2014 Jun 3;111(22):8209-14. doi:, 10.1073/pnas.1404653111. Epub 2014 May 19. PMID:24843144^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.