Relative Respiratory Syncytial Virus Cytopathogenesis in Upper and Lower Respiratory Tract Epithelium

Abstract

RSV induced remarkably similar, albeit quantitatively lower, cytopathogenesis and proinflammatory responses in WD-PNECs compared with WD-PBECs that reproduce many hallmarks of RSV pathogenesis in infants. WD-PNECs may provide an authentic surrogate model with which to study RSV cytopathogenesis in infant airway epithelium.

Infantile respiratory syncytial virus and human rhinovirus infections: respective role in inception and persistence of wheezing

“…In air-liquid interface cultures, generated from nasal and bronchial brushes from healthy preschool children, RSV infection appeared to be localised to apical ciliated epithelial cells, with no detectable infection of goblet cells [37]. RSV-induced apoptosis was associated with epithelial cell sloughing and occasional syncytium formation, which were more noticeable in bronchial than nasal epithelial cell cultures [37]. The cytopathic effect inherent to RSV is permitted and amplified by the presence of a potent but defective host immune response [38].…”

“…Airway epithelial cells appear to be highly permissive to RSV, as demonstrated by the high viral replication and the cell cytotoxicity observed after experimental exposure of human bronchial epithelial cells (BECs) to the virus [36]. In air-liquid interface cultures, generated from nasal and bronchial brushes from healthy preschool children, RSV infection appeared to be localised to apical ciliated epithelial cells, with no detectable infection of goblet cells [37]. RSV-induced apoptosis was associated with epithelial cell sloughing and occasional syncytium formation, which were more noticeable in bronchial than nasal epithelial cell cultures [37].…”

“…1a) [39]. This viral antigen recognition leads to nuclear factor-κB activation with production of interferon (IFN)-β, a type-I IFN, which in turn and via an autocrine mechanism enhances its own synthesis and initiates the production of IFN-α, CXCL8 and type-III IFN (IFN-λ) by airway epithelial cells and innate immune cells [37,39]. These cytokines have the ability to recruit and activate polymorphonuclear leukocytes and natural killer cells and, importantly, also trigger programmed death of infected airway epithelial cells as a mechanism of limiting viral replication and spread to neighbouring cells [39].…”

“…Unfortunately, both RSV nucleoproteins and RSV G-protein can antagonise the immune response to infection ( fig. 2) [37,40,41]. In immortalised cell lines, RSV efficiently suppresses the production of type I IFN using its two unique nonstructural proteins, NS1 and NS2 [40].…”

Antibody-Induced Internalization of the Human Respiratory Syncytial Virus Fusion Protein

“…Among these are three surface glycoproteins, the G glycoprotein, the F protein, and the small hydrophobic (SH) protein (1). The G protein is responsible for attachment with host cells, which are predominantly ciliated airway epithelial cells (7,8). Fusion of the viral and cellular membranes is facilitated by the RSV F protein, as is fusion between the membranes of infected cells with adjacent cells, which result in large, multinucleated syncytia.…”