TY - JOUR
T1 - Fibroblast, Epithelial and Endothelial Cell-Derived Human Cytomegalovirus Strains Display Distinct Neutralizing Antibody Responses and Varying Levels of gH/gL Complexes
AU - Fornara, Chiara
AU - Schultz, Eric
AU - Lilleri, Daniele
AU - Baldanti, Fausto
AU - Ryckman, Brent
AU - Gerna, Giuseppe
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/2/23
Y1 - 2023/2/23
N2 - 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.
AB - 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.
KW - human cytomegalovirus
KW - neutralizing antibodies
KW - pentamer
KW - primary infection
KW - receptors
KW - trimer
KW - Viral Envelope Proteins/genetics
KW - Antibodies, Neutralizing
KW - Cytomegalovirus
KW - Humans
KW - Cytomegalovirus Infections
KW - Membrane Glycoproteins/metabolism
KW - Pregnancy
KW - Endothelial Cells/metabolism
KW - Fibroblasts/metabolism
KW - Female
UR - http://www.scopus.com/inward/record.url?scp=85149962261&partnerID=8YFLogxK
U2 - 10.3390/ijms24054417
DO - 10.3390/ijms24054417
M3 - Article
C2 - 36901847
AN - SCOPUS:85149962261
SN - 1661-6596
VL - 24
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 5
M1 - 4417
ER -