Dynamical Differences in Respiratory Syncytial Virus

Respiratory syncytial virus (RSV) is a leading viral cause of pediatric respiratory infections and early infant mortality. Despite extensive development efforts currently underway, there remain no vaccines available for the prevention of RSV. RSV is an enveloped, negative-strand RNA virus that utilizes two different proteins (G and F) to mediate attachment and entry into host cells. These G and F proteins are the primary determinants of viral strain-specific differences and elicit protective neutralizing antibodies during natural infection in humans. Earlier studies have demonstrated that these proteins play an additional role in regulating the stability of RSV particles in response to temperature and pH. However, it remains unclear how much variability exists in the stability of RSV strains and what contribution changes in temperature and pH make to the clearance of virus during an active infection. In this study, we evaluated the impacts of changes in temperature and pH on the inactivation of four different chimeric recombinant RSV strains that differ exclusively in G and F protein expression. Using these data, we developed predictive mathematical models to examine the specific contributions and variations in susceptibility that exist between viral strains. Our data provide strain-specific clearance rates and temperature-pH landscapes that shed light on the optimal contributions of temperature and pH to viral clearance. These provide new insight into how much variation exists in the clearance of a major respiratory pathogen and may offer new guidance on optimization of viral strains for development of live-attenuated vaccine preparations.