Antigenic Characterization of the HCMV gH/gL/gO and Pentamer Cell Entry Complexes Reveals Binding Sites for Potently Neutralizing Human Antibodies

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Human Cytomegalovirus (HCMV) is a double stranded DNA, enveloped virus infecting >60% of the population worldwide. Typically asymptomatic in healthy adults, HCMV infection causes morbidity and mortality in immunocompromised patients and is the most common viral cause of birth defects in industrialized countries. Despite more than 30 years of research, however, no vaccine against HCMV is available. HCMV utilizes two distinct glycoprotein complexes, gH/gL/gO and gH/gL/UL128/UL130/UL131A (Pentamer), to enter fibroblast and endothelial/epithelial cells, respectively and both are neutralizing antibodies targets. We used orthogonal techniques to study the interaction between gH/gL/gO or Pentamer and a panel of naturally occurring human neutralizing antibodies. The results of this analysis identify three neutralizing epitopes in gH, which are conserved in both glycoproteins complexes, and a different subset of five neutralizing sites in the UL128/Ul130/Ul131A (ULs) portion of the Pentamer. Moreover, EM analysis defines two distinct surfaces targeted by neutralizing antibodies on the ULs suggesting different neutralization mechanisms. Our results reveal regions of the gH/gL/gO and Pentamer complexes important for eliciting strong neutralizing responses in humans and for function in viral entry. Together our data will guide the development of therapeutic monoclonal antibodies and vaccines against HCMV.

Vyšlo v časopise: Antigenic Characterization of the HCMV gH/gL/gO and Pentamer Cell Entry Complexes Reveals Binding Sites for Potently Neutralizing Human Antibodies. PLoS Pathog 11(10): e32767. doi:10.1371/journal.ppat.1005230
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005230

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