Inhibition of human cytomegalovirus entry into mucosal epithelial cells. Antiviral Res 2024 Oct;230:105971
Date
07/30/2024Pubmed ID
39074588Pubmed Central ID
PMC11408113DOI
10.1016/j.antiviral.2024.105971Scopus ID
2-s2.0-85200466040 (requires institutional sign-in at Scopus site)Abstract
Human cytomegalovirus (CMV) causes serious developmental disabilities in newborns infected in utero following oral acquisition by the mother. Thus, neutralizing antibodies in maternal saliva have potential to prevent maternal infection and, consequently, fetal transmission and disease. Based on standard cell culture models, CMV entry mediators (and hence neutralizing targets) are cell type-dependent: entry into fibroblasts requires glycoprotein B (gB) and a trimeric complex (TC) of glycoproteins H, L, and O, whereas endothelial and epithelial cell entry additionally requires a pentameric complex (PC) of glycoproteins H and L with UL128, UL130, and UL131A. However, as the mediators of mucosal cell entry and the potential impact of cellular differentiation remained unclear, the present studies utilized mutant viruses, neutralizing antibodies, and soluble TC-receptor to determine the entry mediators required for infection of mucocutaneus cell lines and primary tonsil epithelial cells. Entry into undifferentiated cells was largely PC-dependent, but PC-independent entry could be induced by differentiation. TC-independent entry was also observed and varied by cell line and differentiation. Infection of primary tonsil cells from some donors was entirely TC-independent. In contrast, an antibody to gB or disruption of virion attachment using heparin blocked entry into all cells. These findings indicate that CMV entry into the spectrum of cell types encountered in vivo is likely to be more complex than has been suggested by standard cell culture models and may be influenced by the relative abundance of virion envelope glycoprotein complexes as well as by cell type, tissue of origin, and state of differentiation.
Author List
He L, Hertel L, James CD, Morgan IM, Klingelhutz AJ, Fu TM, Kauvar LM, McVoy MAAuthor
Li He Postdoctoral Researcher in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Antibodies, NeutralizingAntibodies, Viral
Cell Differentiation
Cell Line
Cells, Cultured
Cytomegalovirus
Cytomegalovirus Infections
Epithelial Cells
Humans
Mucous Membrane
Palatine Tonsil
Viral Envelope Proteins
Virus Internalization
