Stochastic model of BKPy Virus replication and assembly

AbstractBK Polyomavirus (BKPyV), belongs to the same family as SV40 and JC Virus and has recently been associated with both Sjögrens Syndrome and HIV associated Salivary Gland Disease. BKPyV was previously only known for causing the rejection of kidney transplants. As such, BKPyV infection of salivary gland cells implicates oral transmission of the virus. BKPyV replicates slowly in salivary gland cells, producing infectious virus after 72-96 hours. However, it remains unclear how this virus infects or replicates within salivary gland cells, blocking the development of therapeutic strategies to inhibit the virus. Thus, an intracellular, computational model using agent-based modeling was developed to model BKPyV replication within a salivary gland cell. In addition to viral proteins, we modeled host cell machinery that aids transcription, translation and replication of BKPyV. The model has separate cytosolic and nuclear compartments, and represents all large molecules such as proteins, RNAs, and DNA as individual computer “agents” that move and interact within the simulated salivary gland cell environment. An application of the Boids algorithm was implemented to simulate molecular binding and formation of BKPyV virions and BKPyV virus-like particles (VLPs). This approach enables the direct study of spatially complex processes such as BKPyV virus self-assembly, transcription, and translation. This model reinforces experimental results implicating the processes that result in the slow accumulation of viral proteins. It revealed that the slow BKPyV replication rate in salivary gland cells might be explained by capsid subunit accumulation rates. BKPyV particles may only form after large concentrations of capsid subunits have accumulated. In addition, salivary gland specific transcription factors may enable early region transcription of BKPyV.

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Breast Cancer Exosome-like Microvesicles and Salivary Gland Cells Interplay Alters Salivary Gland Cell-Derived Exosome-like Microvesicles In Vitro

PLoS ONE ◽

10.1371/journal.pone.0033037 ◽

2012 ◽

Vol 7 (3) ◽

pp. e33037 ◽

Cited By ~ 61

Author(s):

Chang S. Lau ◽

David T. W. Wong

Keyword(s):

Breast Cancer ◽

Salivary Gland ◽

Gland Cell ◽

Salivary Gland Cell ◽

Gland Cells ◽

Salivary Gland Cells

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Non-Lethal Concentration of MeHg Causes Marked Responses in the DNA Repair, Integrity, and Replication Pathways in the Exposed Human Salivary Gland Cell Line

Frontiers in Pharmacology ◽

10.3389/fphar.2021.698671 ◽

2021 ◽

Vol 12 ◽

Author(s):

Lygia Sega Nogueira ◽

Carolina P. Vasconcelos ◽

Jessica Rodrigues Plaça ◽

Geovanni Pereira Mitre ◽

Leonardo Oliveira Bittencourt ◽

...

Keyword(s):

Dna Repair ◽

Salivary Gland ◽

Cell Line ◽

Gland Cell ◽

Salivary Gland Cell ◽

Human Salivary Gland ◽

Gland Cells ◽

Salivary Gland Cells

In Brazilian northern Amazon, communities are potentially exposed and vulnerable to methylmercury (MeHg) toxicity through the vast ingestion of fish. In vivo and in vitro studies demonstrated that the salivary glands as a susceptible organ to this potent environmental pollutant, reporting alterations on physiological, biochemical, and proteomic parameters. However, the alterations caused by MeHg on the gene expression of the exposed human salivary gland cells are still unknown. Therefore, the goal was to perform the transcriptome profile of the human salivary gland cell line after exposure to MeHg, using the microarray technique and posterior bioinformatics analysis. The cell exposure was performed using 2.5 µM MeHg. A previously published study demonstrated that this concentration belongs to a range of concentrations that caused biochemical and metabolic alterations in this linage. As a result, the MeHg exposure did not cause lethality in the human salivary gland cells line but was able to alter the expression of 155 genes. Downregulated genes (15) are entirety relating to the cell metabolism impairment, and according to KEGG analysis, they belong to the glycosphingolipid (GSL) biosynthesis pathway. On the other hand, most of the 140 upregulated genes were related to cell-cycle progression, DNA repair, and replication pathway, or cellular defenses through the GSH basal metabolism. These genomic changes revealed the effort to the cell to maintain physiological and genomic stability to avoid cell death, being in accordance with the nonlethality in the toxicity test. Last, the results support in-depth studies on nonlethal MeHg concentrations for biomarkers identification that interpret transcriptomics data in toxicological tests serving as an early alert of physiological changes in vitro biological models.

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AnIn VitroCulture System for Long-Term Expansion of Epithelial and Mesenchymal Salivary Gland Cells: Role of TGF-β1 in Salivary Gland Epithelial and Mesenchymal Differentiation

BioMed Research International ◽

10.1155/2013/815895 ◽

2013 ◽

Vol 2013 ◽

pp. 1-20 ◽

Cited By ~ 9

Author(s):

Kajohnkiart Janebodin ◽

Worakanya Buranaphatthana ◽

Nicholas Ieronimakis ◽

Aislinn L. Hays ◽

Morayma Reyes

Keyword(s):

Salivary Gland ◽

Culture System ◽

Gland Cell ◽

Mesenchymal Cells ◽

Salivary Gland Cell ◽

Salivary Gland Cells ◽

Gland Development

Despite a pivotal role in salivary gland development, homeostasis, and disease, the role of salivary gland mesenchyme is not well understood. In this study, we used theCol1a1-GFPmouse model to characterize the salivary gland mesenchymein vitroandin vivo. TheCol1a1-GFPtransgene was exclusively expressed in the salivary gland mesenchyme.Ex vivoculture of mixed salivary gland cells in DMEM plus serum medium allowed long-term expansion of salivary gland epithelial and mesenchymal cells. The role of TGF-β1 in salivary gland development and disease is complex. Therefore, we used thisin vitroculture system to study the effects of TGF-β1 on salivary gland cell differentiation. TGF-β1 induced the expression of collagen, and inhibited the formation of acini-like structures in close proximity to mesenchymal cells, which adapted a fibroblastic phenotype. In contrast, TGF-βR1 inhibition increased acini genes and fibroblast growth factors (Fgf-7andFgf-10), decreased collagen and induced formation of larger, mature acini-like structures. Thus, inhibition of TGF-βsignaling may be beneficial for salivary gland differentiation; however, due to differential effects of TGF-β1 in salivary gland epithelial versus mesenchymal cells, selective inhibition is desirable. In conclusion, this mixed salivary gland cell culture system can be used to study epithelial-mesenchymal interactions and the effects of differentiating inducers and inhibitors.

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Novel Modeling Approach to Generate a Polymeric Nanofiber Scaffold for Salivary Gland Cells

Journal of Nanotechnology in Engineering and Medicine ◽

10.1115/1.4001744 ◽

2010 ◽

Vol 1 (3) ◽

Cited By ~ 24

Author(s):

Riffard Jean-Gilles ◽

David Soscia ◽

Sharon Sequeira ◽

Michael Melfi ◽

Anand Gadre ◽

...

Keyword(s):

Salivary Gland ◽

Gland Cell ◽

Self Organization ◽

Salivary Gland Cell ◽

Nanofiber Scaffold ◽

Salivary Gland Tissue ◽

Salivary Gland Cells ◽

Gland Tissue ◽

Nanofiber Scaffolds ◽

Tissue Construct

Electrospun nanofibers have been utilized in many biomedical applications as biomimetics of extracellular matrix proteins that promote self-organization of cells into 3D tissue constructs. As progress toward an artificial salivary gland tissue construct, we prepared nanofiber scaffolds using PLGA, which is a biodegradable and biocompatible material. We used electrospinning to prepare nanofiber scaffolds using poly(lactic-co-glycolic acid) (PLGA) with both dimethylformamide (DMF) and hexafluoroisopropanol (HFIP) as solvents. Using a design of experiment approach, the system and process parameters were optimized concurrently, and their effects on the diameter of the resulting fibers were computed into a single model. A transfer function was used to reproducibly produce nanofibers of a defined diameter, which was confirmed by a scanning electron microscope. The salivary gland cell line was seeded on the nanofiber scaffolds, and morphology, cell proliferation, and viability were assayed. Varying two or more parameters simultaneously yielded trends diverging from the linear response predicted by previous studies. Comparison of two solvents revealed that the diameter of PLGA nanofibers generated using HFIP is less sensitive to changes in the system and process parameters than are fibers generated using DMF. Inclusion of NaCl reduced morphological inconsistencies and minimized process variability. The resulting nanofiber scaffolds supported attachment, survival, and cell proliferation of a mouse salivary gland epithelial cell line. In comparison with glass and flat PLGA films, the nanofibers promoted self-organization of the salivary gland cells into 3D cell clusters, or aggregates. These data indicate that nanofiber scaffolds promote salivary gland cell organization, and suggest that a nanofiber scaffold could provide a platform for engineering of an artificial salivary gland tissue construct. This study additionally provides a method for efficient production of nanofiber scaffolds for general application in tissue engineering.

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