Membrane microdomains as therapeutic targets to control respiratory syncytial virus

Respiratory syncytial virus (RSV) infects most individuals by the age of two years old with reinfections occurring throughout life. RSV causes a wide spectrum of disease, contributing to high rates of morbidity and mortality in very young, elderly, and immunocompromised individuals. Severe RSV infections have been linked to an excessive and deleterious host immune response that can lead to pulmonary complications such as bronchiolitis. There are currently no established vaccines against RSV, and new treatments for infection are still in development and not established in routine practice. Membrane microdomains (MM) are specialised regions of host cell membranes that play crucial roles in inflammatory cell signalling and are utilised as platforms for the adsorption and infection of enveloped viruses such as RSV. Previous studies have reported that a naturally occurring phosphatidylserine lipid species, SAPS, can perturb MM and the associated proinflammatory response induced by rhinovirus. I hypothesised that SAPS may be used to disrupt MM, modulating the immune response and the life cycle of RSV in airway epithelial cells (AEC)s. I further hypothesised that SAPS inhibitory effects may also prevent subsequent bacterial co-infection in RSV-infected cells. AECs were infected with RSV and incubated with SAPS either during infection or at a range of times post-infection. RSV infected AECs co-incubated with SAPS exhibited significantly decreased release of CXCL8 and CCL5 up to 48 hours when compared to untreated cells alone or RSV infected cells co-incubated with the comparative liposome PAPC. Furthermore, AECs infected with RSV in the presence of SAPS had significantly reduced numbers of infected cells and subsequent viral replication in comparison to controls. Preliminary data has also demonstrated that SAPS can significantly reduce the adhesion of Streptococcus pneumoniae to AECs directly and inhibit subsequent adhesion in RSV-infected cells. These data demonstrate that SAPS may have potential therapeutic value as a prophylactic treatment to modulate both RSV infection of AECs and the ensuing inflammatory response.