Fibroblast, Epithelial and Endothelial Cell-Derived Human Cytomegalovirus Strains Display Distinct Neutralizing Antibody Responses and Varying Levels of gH/gL Complexes

Chiara Fornara, Eric Schultz, Daniele Lilleri, Fausto Baldanti, Brent Ryckman, Giuseppe Gerna

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

In sequential sera from pregnant women with HCMV primary infection (PI), the serum neutralizing activity is higher against virions produced in epithelial and endothelial cells than in fibroblasts. Immunoblotting shows that the pentamer complex/trimer complex (PC/TC) ratio varies according to the producer cell culture type used for the virus preparation to be employed in the neutralizing antibody (NAb) assay, and is lower in fibroblasts and higher in epithelial, and especially endothelial cells. The blocking activity of TC- and PC-specific inhibitors varies according to the PC/TC ratio of virus preparations. The rapid reversion of the virus phenotype following its back passage to the original cell culture (fibroblasts) potentially argues in favor of a producer cell effect on virus phenotype. However, the role of genetic factors cannot be overlooked. In addition to the producer cell type, the PC/TC ratio may differ in single HCMV strains. In conclusion, the NAb activity not only varies with different HCMV strains, but is a dynamic parameter changing according to virus strain, type of target and producer cells, and number of cell culture passages. These findings may have some important implications for the development of both therapeutic antibodies and subunit vaccines.

Original languageEnglish
Article number4417
JournalInternational Journal of Molecular Sciences
Volume24
Issue number5
DOIs
StatePublished - Feb 23 2023

Keywords

  • human cytomegalovirus
  • neutralizing antibodies
  • pentamer
  • primary infection
  • receptors
  • trimer
  • Viral Envelope Proteins/genetics
  • Antibodies, Neutralizing
  • Cytomegalovirus
  • Humans
  • Cytomegalovirus Infections
  • Membrane Glycoproteins/metabolism
  • Pregnancy
  • Endothelial Cells/metabolism
  • Fibroblasts/metabolism
  • Female

Fingerprint

Dive into the research topics of 'Fibroblast, Epithelial and Endothelial Cell-Derived Human Cytomegalovirus Strains Display Distinct Neutralizing Antibody Responses and Varying Levels of gH/gL Complexes'. Together they form a unique fingerprint.

Cite this