scholarly journals Soluble Human Cytomegalovirus gH/gL/pUL128–131 Pentameric Complex, but Not gH/gL, Inhibits Viral Entry to Epithelial Cells and Presents Dominant Native Neutralizing Epitopes

2015 ◽  
Vol 290 (26) ◽  
pp. 15985-15995 ◽  
Author(s):  
John W. Loughney ◽  
Richard R. Rustandi ◽  
Dai Wang ◽  
Matthew C. Troutman ◽  
Lawrence W. Dick ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Human Cytomegalovirus ◽  
Viral Entry ◽  
Neutralizing Epitopes

scholarly journals Genome sequences of human cytomegalovirus strain TB40/E variants propagated in fibroblasts and epithelial cells

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Ahmed Al Qaffas ◽  
Salvatore Camiolo ◽  
Mai Vo ◽  
Alexis Aguiar ◽  
Amine Ourahmane ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Human Cytomegalovirus ◽  
Viral Entry ◽  
Sequence Data ◽  
Laboratory Strain ◽  
Serial Passage ◽  
Wild Type Virus ◽  
Protein Coding ◽  
Genetic Changes ◽  
Long Read

AbstractThe advent of whole genome sequencing has revealed that common laboratory strains of human cytomegalovirus (HCMV) have major genetic deficiencies resulting from serial passage in fibroblasts. In particular, tropism for epithelial and endothelial cells is lost due to mutations disrupting genes UL128, UL130, or UL131A, which encode subunits of a virion-associated pentameric complex (PC) important for viral entry into these cells but not for entry into fibroblasts. The endothelial cell-adapted strain TB40/E has a relatively intact genome and has emerged as a laboratory strain that closely resembles wild-type virus. However, several heterogeneous TB40/E stocks and cloned variants exist that display a range of sequence and tropism properties. Here, we report the use of PacBio sequencing to elucidate the genetic changes that occurred, both at the consensus level and within subpopulations, upon passaging a TB40/E stock on ARPE-19 epithelial cells. The long-read data also facilitated examination of the linkage between mutations. Consistent with inefficient ARPE-19 cell entry, at least 83% of viral genomes present before adaptation contained changes impacting PC subunits. In contrast, and consistent with the importance of the PC for entry into endothelial and epithelial cells, genomes after adaptation lacked these or additional mutations impacting PC subunits. The sequence data also revealed six single noncoding substitutions in the inverted repeat regions, single nonsynonymous substitutions in genes UL26, UL69, US28, and UL122, and a frameshift truncating gene UL141. Among the changes affecting protein-coding regions, only the one in UL122 was strongly selected. This change, resulting in a D390H substitution in the encoded protein IE2, has been previously implicated in rendering another viral protein, UL84, essential for viral replication in fibroblasts. This finding suggests that IE2, and perhaps its interactions with UL84, have important functions unique to HCMV replication in epithelial cells.

scholarly journals Genome sequences of human cytomegalovirus strain TB40/E variants propagated in fibroblasts and epithelial cells

2021 ◽  
Author(s):  
Ahmed Al Qaffas ◽  
Salvatore Camiolo ◽  
Mai Vo ◽  
Alexis Aguiar ◽  
Amine Ourahmane ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Human Cytomegalovirus ◽  
Viral Entry ◽  
Sequence Data ◽  
Laboratory Strain ◽  
Serial Passage ◽  
Wild Type Virus ◽  
Protein Coding ◽  
Genetic Changes ◽  
Long Read

Abstract The advent of whole genome sequencing has revealed that common laboratory strains of human cytomegalovirus (HCMV) have major genetic deficiencies resulting from serial passage in fibroblasts. In particular, tropism for epithelial and endothelial cells is lost due to mutations disrupting genes UL128, UL130, or UL131A, which encode subunits of a virion-associated pentameric complex (PC) important for viral entry into these cells but not for entry into fibroblasts. The endothelial cell-adapted strain TB40/E has a relatively intact genome and has emerged as a laboratory strain that closely resembles wild-type virus. However, several heterogeneous TB40/E stocks and cloned variants exist that display a range of sequence and tropism properties. Here, we report the use of PacBio sequencing to elucidate the genetic changes that occurred, both at the consensus level and within subpopulations, upon passaging a TB40/E stock on ARPE-19 epithelial cells. The long-read data also facilitated examination of the linkage between mutations. Consistent with inefficient ARPE-19 cell entry, at least 83% of viral genomes present before adaptation contained changes impacting PC subunits. In contrast, and consistent with the importance of the PC for entry into endothelial and epithelial cells, genomes after adaptation lacked these or additional mutations impacting PC subunits. The sequence data also revealed six single noncoding substitutions in the inverted repeat regions, single nonsynonymous substitutions in genes UL26, UL69, US28, and UL122, and a frameshift truncating gene UL141. Among the changes affecting protein-coding regions, only the one in UL122 was strongly selected. This change, resulting in a D390H substitution in the encoded protein IE2, has been previously implicated in rendering another viral protein, UL84, essential for viral replication in fibroblasts. This finding suggests that IE2, and perhaps its interactions with UL84, have important functions unique to HCMV replication in epithelial cells.

scholarly journals Human Cytomegalovirus Glycoprotein gO Complexes with gH/gL, Promoting Interference with Viral Entry into Human Fibroblasts but Not Entry into Epithelial Cells

2011 ◽  
Vol 85 (22) ◽  
pp. 11638-11645 ◽  
Author(s):  
A. L. Vanarsdall ◽  
M. C. Chase ◽  
D. C. Johnson
Keyword(s):  
Epithelial Cells ◽  
Human Cytomegalovirus ◽  
Viral Entry ◽  
Human Fibroblasts

scholarly journals Human Cytomegalovirus Infection of Caco-2 Cells Occurs at the Basolateral Membrane and Is Differentiation State Dependent

1999 ◽  
Vol 73 (6) ◽  
pp. 4552-4560 ◽  
Author(s):  
Michael A. Jarvis ◽  
C. Edward Wang ◽  
Heather L. Meyers ◽  
Patricia P. Smith ◽  
Christopher L. Corless ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Human Cytomegalovirus ◽  
Viral Entry ◽  
Hcmv Infection ◽  
Cell Model ◽  
Basolateral Membrane ◽  
In Vitro Models

ABSTRACT Epithelial cells are known to be a major target for human cytomegalovirus (HCMV) infection; however, the analysis of virus-cell interactions has been difficult to approach due to the lack of in vitro models. In this study, we established a polarized epithelial cell model using a colon epithelial cell-derived cell line (Caco-2) that is susceptible to HCMV infection at early stages of cellular differentiation. Infection of polarized cells was restricted to the basolateral surface whereas virus was released apically, which was consistent with the apical and not basolateral surface localization of two essential viral glycoproteins, gB and gH. HCMV infection resulted in the development of a cytopathology characteristic of HCMV infection of colon epithelium in vivo, and infection did not spread from cell to cell. The inability of HCMV to infect Caco-2 cells at late stages of differentiation was due to a restriction at the level of viral entry and was consistent with the sequestration of a cellular receptor for HCMV. These observations provide the first evidence that restriction of HCMV replication in epithelial cells is due to a receptor-mediated phenomenon.

scholarly journals Peptides from cytomegalovirus UL130 and UL131 proteins induce high titer antibodies that block viral entry into mucosal epithelial cells

Vaccine ◽  
2011 ◽  
Vol 29 (15) ◽  
pp. 2705-2711 ◽  
Author(s):  
Frances M. Saccoccio ◽  
Anne L. Sauer ◽  
Xiaohong Cui ◽  
Amy E. Armstrong ◽  
EL-Sayed E. Habib ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Viral Entry ◽  
High Titer

scholarly journals Human Cytomegalovirus Circumvents NF-κB Dependence in Retinal Pigment Epithelial Cells

2001 ◽  
Vol 167 (4) ◽  
pp. 1900-1908 ◽  
Author(s):  
Jindrich Cinatl ◽  
Stefan Margraf ◽  
Jens-Uwe Vogel ◽  
Martin Scholz ◽  
Jaroslav Cinatl ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Human Cytomegalovirus ◽  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Pigment Epithelial ◽  
Pigment Epithelial Cells

scholarly journals Disruption of Adherens Junctions Liberates Nectin-1 To Serve as Receptor for Herpes Simplex Virus and Pseudorabies Virus Entry

2002 ◽  
Vol 76 (14) ◽  
pp. 7203-7208 ◽  
Author(s):  
Miri Yoon ◽  
Patricia G. Spear
Keyword(s):  
Herpes Simplex ◽  
Epithelial Cells ◽  
Viral Entry ◽  
Pseudorabies Virus ◽  
Adherens Junctions ◽  
Cell Junctions ◽  
Immunoglobulin Superfamily ◽  
Calcium Depletion ◽  
Normal Medium ◽  
Herpes Simplex Viruses

ABSTRACT Nectin-1, a cell adhesion molecule belonging to the immunoglobulin superfamily, can bind to virion glycoprotein D (gD) to mediate entry of herpes simplex viruses (HSV) and pseudorabies virus (PRV). Nectin-1 colocalizes with E-cadherin at adherens junctions in epithelial cells. The disruption of cell junctions can result in the redistribution of nectin-1. To determine whether disruption of junctions by calcium depletion influenced the susceptibility of epithelial cells to viral entry, Madin-Darby canine kidney cells expressing endogenous nectin-1 or transfected human nectin-1 were tested for the ability to bind soluble forms of viral gD and to be infected by HSV and PRV, before and after calcium depletion. Confocal microscopy revealed that binding of HSV and PRV gD was localized to adherens junctions in cells maintained in normal medium but was distributed, along with nectin-1, over the entire cell surface after calcium depletion. Both the binding of gD and the fraction of cells that could be infected by HSV-1 and PRV were enhanced by calcium depletion. Taken together, these results provide evidence that nectin-1 confined to adherens junctions in epithelial cells is not very accessible to virus, whereas dissociation of cell junctions releases nectin-1 to serve more efficiently as an entry receptor.

scholarly journals Cytomegalovirus, Macrophages and Breast Cancer

2017 ◽  
Vol 11 (1) ◽  
pp. 15-27 ◽  
Author(s):  
S. Pasquereau ◽  
F. Al Moussawi ◽  
W. Karam ◽  
M. Diab Assaf ◽  
A. Kumar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Human Cytomegalovirus ◽  
Breast Tumor ◽  
Poor Prognosis ◽  
Tumor Tissue ◽  
Tumor Associated Macrophages ◽  
Potential Implication ◽  
Breast Tumor Tissue

The human cytomegalovirus (HCMV) is a betaherpesvirus that is highly host specific, infects among others epithelial cells and macrophages, and has been recently mentioned as having oncomodulatory properties. HCMV is detected in the breast tumor tissue where macrophages, especially tumor associated macrophages, are associated with a poor prognosis. In this review, we will discuss the potential implication of HCMV in breast cancer with emphasis on the role played by macrophages.

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