A quantitative assessment of dynamical differences of RSV infections in vitro and in vivo

Abstract

Experimental results in vitro and in animal models are used to guide researchers in testing vaccines or treatment in humans. However, viral kinetics are different in vitro, in animals, and in humans, so it is sometimes difficult to translate results from one system to another. In this study, we use a mathematical model to fit experimental data from multiple cycle respiratory syncytial virus (RSV) infections in vitro, in african green monkey (AGM), and in humans in order to quantitatively compare viral kinetics in the different systems. We find that there are differences in viral clearance rate, productively infectious cell lifespan, and eclipse phase duration between in vitro and in vivo systems and among different in vivo systems. We show that these differences in viral kinetics lead to different estimates of drug effectiveness of fusion inhibitors in vitro and in AGM than in humans.

Dynamical Differences in Respiratory Syncytial Virus

“…We fit the viral replication data to a viral kinetics model used in Baccam et al. ( 2006 ), González-Parra and Dobrovolny ( 2018 ) and Pinilla et al. ( 2012 ), V is the virus population (in f.f.u./mL) as a function of time t (in days).…”

“… 2006 ). Recently, mathematical models have also be generated for RSV that predict both in vitro and in vivo replication dynamics (González-Parra and Dobrovolny 2019 , 2018 ). However, the recent discovery of appreciable differences in stability between RSV strains led us to hypothesize that both temperature and pH also play important strain-specific roles in viral clearance of RSV infection.…”

Quantifying the effect of trypsin and elastase on in vitro SARS-CoV infections

“…We use a within host model of viral infection with the method of stages to generate gamma distributions for the cell transitions from eclipse to infectious and infectious to dead. This model has previously been used to analyse other respiratory infections such as influenza ( Pinilla et al, 2012 , Paradis et al, 2015 , Beggs and Dobrovolny, 2015 , González-Parra et al, 2018 ), and RSV ( González-Parra et al, 2018 , González-Parra and Dobrovolny, 2018 ). The system of differential equations is where the target cells T are infected by the virus V at an infection rate β .…”

Role of Respiratory Syncytial Virus in Pediatric Pneumonia

“…The already cited prospective viral surveillance study of Khuri-Bulos and colleagues reported a significantly lower presence of fever but a high probability of cough, shortness of breath, and flaring in patients with RSV infection [58]. It has been observed that RSV-A causes more severe illness than RSV-B; in fact, the two serotypes elicit a different response in terms of cytokine and neutrophil production [74,79].…”

“…These infections can appear every two or three years, with different clinical RSV presents direct cytopathic activity, but signs and symptoms, which are virus dependent, are also due to the local host inflammatory response (innate and adaptative immune responses) created by its presence in airway epithelial cells [69][70][71][72][73]. Many in vitro and animal models have been employed to infer the pathological pathway of RSV, though its interaction with human hosts, and particularly with children, differs greatly from other models [74].…”