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

Virology. 2018 Oct:523:129-139. doi: 10.1016/j.virol.2018.07.027. Epub 2018 Aug 23.

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.

Keywords: African green monkey; Elderly; Fusion inhibitor; Mathematical model; Pediatric; Respiratory syncytial virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Child
  • Chlorocebus aethiops
  • Gene Expression
  • Host Specificity
  • Humans
  • Lung / drug effects
  • Lung / pathology
  • Lung / virology
  • Membrane Fusion / drug effects
  • Models, Statistical*
  • Respiratory Syncytial Virus Infections / drug therapy*
  • Respiratory Syncytial Virus Infections / pathology
  • Respiratory Syncytial Virus Infections / virology
  • Respiratory Syncytial Virus, Human / drug effects*
  • Respiratory Syncytial Virus, Human / genetics
  • Respiratory Syncytial Virus, Human / growth & development
  • Respiratory Syncytial Virus, Human / metabolism
  • Viral Fusion Protein Inhibitors / therapeutic use*
  • Viral Fusion Proteins / antagonists & inhibitors*
  • Viral Fusion Proteins / genetics
  • Viral Fusion Proteins / metabolism
  • Viral Load / drug effects
  • Virus Internalization / drug effects*
  • Virus Replication / drug effects

Substances

  • Viral Fusion Protein Inhibitors
  • Viral Fusion Proteins