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

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 pro...

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Bibliographic Details
Published in:International journal of molecular sciences 2023-02, Vol.24 (5), p.4417
Main Authors: Fornara, Chiara, Schultz, Eric, Lilleri, Daniele, Baldanti, Fausto, Ryckman, Brent, Gerna, Giuseppe
Format: Article
Language:English
Subjects:
Antibodies
Antibodies, Neutralizing
Cell culture
Computer software industry
Cytomegalovirus
Cytomegalovirus Infections
Endothelial cells
Endothelial Cells - metabolism
Endothelium
Female
Fibroblasts
Fibroblasts - metabolism
Genetic factors
Glycoproteins
Health aspects
Humans
Immunoblotting
Infection
Infections
Membrane Glycoproteins - metabolism
Neutralizing
Phenotypes
Pregnancy
Pregnant women
Producer cells
Reversion
Strains (organisms)
Viral antibodies
Viral Envelope Proteins - genetics
Virions
Viruses
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms24054417