Mechanism for neutralizing activity by the anti-CMV gH/gL monoclonal antibody MSL-109.

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