Progressive Changes in Inflammatory and Matrix Adherence of Bronchial Epithelial Cells with Persistent Respiratory Syncytial Virus (RSV) Infection (Progressive Changes in RSV Infection)

Abstract

In addition to the acute manifestations of respiratory syncytial virus (RSV), persistent infection may be associated with long-term complications in the development of chronic respiratory diseases. To understand the mechanisms underlying RSV-induced long-term consequences, we established an in vitro RSV (strain A2) infection model using human bronchial epithelial (16HBE) cells that persists over four generations and analyzed cell inflammation and matrix adherence. Cells infected with RSV at multiplicity of infection (MOI) 0.0067 experienced cytolytic or abortive infections in the second generation (G2) or G3 but mostly survived up to G4. Cell morphology, leukocyte and matrix adherence of the cells did not change in G1 or G2, but subsequently, leukocyte adherence and cytokine/chemokine secretion, partially mediated by intercellular adhesion molecule-1 (ICAM-1), increased drastically, and matrix adherence, partially mediated by E-cadherin, decreased until the cells died. Tumor necrosis factor-α (TNF-α) secretion was inhibited by ICAM-1 antibody in infected-16HBE cells, suggesting that positive feedback between TNF-α secretion and ICAM-1 expression may be significant in exacerbated inflammation. These data demonstrate the susceptibility of 16HBE cells to RSV and their capacity to produce long-term progressive RSV infection, which may contribute to inflammation mobilization and epithelial shedding.

Persistent Transmissible Gastroenteritis Virus Infection Enhances Enterotoxigenic Escherichia coli K88 Adhesion by Promoting Epithelial-Mesenchymal Transition in Intestinal Epithelial Cells

“…Supernatants from cells with persistent infection produced virus plaques at a reduced level, perhaps due to the generation of defective interfering particles (DIPs) (20,21). Persistent infection by respiratory syncytial virus (RSV) and coxsackie B virus (CVB) upregulates adhesion molecules and proinflammatory cytokines (22,23).…”

Comparison of miRNA profiling during airway epithelial repair in undifferentiated and differentiated cells in vitro

“…Although these cells are not fully differentiated, previous studies showed that 16HBE14o-cell line can be a promising alternative to primary NHBE in some experimental models e.g. in virus infection studies (Liu et al 2013). …”

Downregulation of matrix metalloproteinase-19 induced by respiratory syncytial viral infection affects the interaction between epithelial cells and fibroblasts

“…Following 2 days in culture, the cells at 90% confluence were infected with RSV at a multiplicity of infection (MOI) of 0.01. The infected cells were collected after 3 days, when the cells exhibited a healthy cell monolayer morphology ( 10 ), and after 7 days, when a number of small syncytia began to form. In addition, a separate group of 16HBE cells were treated using the same procedure, but with uninfected HeLa cell lysate, and were used as a mock control group.…”

“…The airway epithelium is central in initiating pulmonary inflammation, particularly in the case of RSV, as this virus productively replicates only in the respiratory mucosa ( 4 , 5 ). Enzymes involved in degradation of the extracellular matrix, which have a number of important physiological effects, including remodeling of the extracellular matrix, facilitating cell migration, cleaving cytokines and activating defensins, may be important in initiating pulmonary diseases ( 6 , 7 ).…”