Comparative neutralizing potencies of antibodies suggest conservation as well as mechanistic differences in human cytomegalovirus entry into epithelial and endothelial cells. Virol J 2020 Apr 08;17(1):50
Date
04/10/2020Pubmed ID
32268919Pubmed Central ID
PMC7144056DOI
10.1186/s12985-020-01320-2Scopus ID
2-s2.0-85083191600 (requires institutional sign-in at Scopus site) 3 CitationsAbstract
Antibody neutralization of cytomegalovirus (CMV) entry into diverse cell types is a key consideration for development of vaccines and immunotherapeutics. CMV entry into fibroblasts differs significantly from entry into epithelial or endothelial cells: fibroblast entry is mediated by gB and gH/gL/gO, whereas both epithelial and endothelial cell entry require an additional pentameric complex (PC) comprised of gH/gL/UL128/UL130/UL131A. Because PC-specific antibodies in CMV-seropositive human sera do not affect fibroblast entry but potently block entry into epithelial or endothelial cells, substantially higher neutralizing potencies for CMV-positive sera are observed when assayed using epithelial cells as targets than when using fibroblasts. That certain sera exhibit similar discordances between neutralizing potencies measured using epithelial vs. endothelial cells (Gerna G. et al.J Gen Virol, 89:853-865, 2008) suggested that additional mechanistic differences may also exist between epithelial and endothelial cell entry. To further explore this issue, neutralizing potencies using epithelial and endothelial cells were simultaneously determined for eight CMV-positive human sera, CMV-hyperimmune globulin, and a panel of monoclonal or anti-peptide antibodies targeting specific epitopes in gB, gH, gH/gL, or the PC. No significant differences were observed between epithelial and endothelial neutralizing potencies of epitope-specific antibodies, CMV-hyperimmune globulin, or seven of the eight human sera. However, one human serum exhibited a six-fold higher potency for neutralizing entry into epithelial cells vs. endothelial cells. These results suggest that epitopes exist that are important for epithelial entry but are less critical, or perhaps dispensable, for endothelial cell entry. Their existence should be considered when developing monoclonal antibody therapies or subunit vaccines representing limited epitopes.
Author List
Qi Y, He L, Cui X, Hertel L, Freed DC, Fu TM, Kauvar LM, McVoy MA, Ruan QAuthor
Li He Postdoctoral Researcher in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntibodies, Neutralizing
Antibodies, Viral
Cell Line
Cytomegalovirus
Endothelial Cells
Epithelial Cells
Epitopes
Humans
Inhibitory Concentration 50
Neutralization Tests
Rabbits
Virus Internalization
