Respiratory Syncytial Virus F and G Proteins Induce Interleukin 1α, CC, and CXC Chemokine Responses by Normal Human Bronchoepithelial Cells

Abstract

Human respiratory syncytial virus (RSV) is a ubiquitous respiratory virus causing serious lower respiratory tract disease in infants and young children worldwide. Studies have shown that RSV infection modulates chemokine expression patterns suggesting that particular cytokine expression profiles may be indicators of disease severity. In this study, we show that RSV F or G protein treatment of fully differentiated primary human bronchial epithelial (NHBE) cells induces apical and basolateral secretion of IL-8, IP-10, MCP-1, and RANTES. Purified RSV G (attachment) protein was shown to stimulate the secretion of IL-1α, and RANTES, while purified F (fusion) protein elicited the production of IL-8, IP-10, and RANTES. Studies with UV-inactivated RSV showed that treatment of NHBE cells induces apical IL-8, IP-10, and MCP-1 secretion independent of infection suggesting that RSV proteins alone modify the chemokine response pattern which may affect the early immune response prior to infection.

Ciliary dyskinesia is an early feature of respiratory syncytial virus infection

“…Furthermore, neutrophils are thought to augment RSV-induced epithelial damage [24,25], and the absence of these cells in our system may explain the lack of observed cytopathology. Ciliated cell cultures also show an elevated production of the IFN-cinduced protein CXCL10 following RSV infection, which is consistent with previous studies [26]. Interestingly, we did not find a significant increase in the level of IFN-c following RSV infection.…”

“…Studies suggest that the secretion of cytokines following RSV infection is predominantly in the basolateral direction, and significant increases in basolateral levels of IL-6 [3,7,28], CXCL8 [3,7,28], CXCL10 [3] and RANTES (regulated on activation, normal T-cell expressed and secreted) [7] have been reported. There are also reports of increased apical secretion of IL-1a [26], CXCL8 [6,26], CXCL10 [26], CCL2 [26] and RANTES [6,26] following RSV infection of differentiated primary human respiratory epithelial cells cultured at ALI. These studies measured cytokine production at different time-points, ranging from 24 h to 72 h post-RSV infection.…”

Mutating the CX3C Motif in the G Protein Should Make a Live Respiratory Syncytial Virus Vaccine Safer and More Effective

“…A potential role for the G protein-CX3CR1 interaction in RSV disease is indicated by studies showing the G protein's substantial influence on host responses to infection and disease pathogenesis. In in vitro studies, the RSV G protein has been noted to stimulate AEC responses and to dampen macrophage and dendritic cell responses (38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48). In vivo in mice, RSV G protein has been associated with increased weight loss, numbers of pulmonary inflammatory cells, levels of pulmonary mucus and Th2 cytokines, airway obstruction, and enhanced respiratory disease in RSV-challenged, FI-RSVvaccinated mice (18,20,21,26,31,(48)(49)(50)(51).…”

In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo

“…In this regard, the recent advent of technology to culture primary human airway epithelial cells into physiologically authentic pseudostratified airway epithelial (HAE) cultures is very attractive (16). Indeed, such cultures already have been used to study a number of respiratory virus-host interactions, including RSV (17)(18)(19)(20)(21)(22)(23).…”