DOI: 10.1101/451302Oct 24, 2018Paper

Mathematical Modeling Identifies the Role of Adaptive Immunity as a Key Controller of Respiratory Syncytial Virus (RSV) Titer in Cotton Rats

BioRxiv : the Preprint Server for Biology
Darren WethingtonJayajit Das


Respiratory syncytial virus (RSV) is a common virus that can have varying effects ranging from mild cold-like symptoms to mortality depending on the age and immune status of the individual. We combined mathematical modeling using ordinary differential equations (ODEs) with measurement of RSV infection kinetics in primary well differentiated human airway epithelial (HAE) cultures in vitro and in immunocompetent and immunosuppressed cotton rats to glean mechanistic details that underlie RSV infection kinetics in the lung. Quantitative analysis of viral titer kinetics in our mathematical model showed that the elimination of infected cells by the adaptive immune response generates unique RSV titer kinetic features including a faster time scale of viral titer clearance than viral production, and a monotonic decrease in the peak RSV titer with decreasing inoculum dose. Parameter estimation in the ODE model using a non-linear mixed effects approach revealed a very low rate (average single cell lifetime > 10 days) of cell lysis by RSV before the adaptive immune response is initiated. Our model predicted negligible changes in the RSV titer kinetics on earlier days (< 5 d.p.i) but a slower decay in RSV titer at later days (>5 d.p.i) in i...Continue Reading

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