Model-based inference from multiple dose, time course data reveals Wolbachia effects on infection profiles of type 1 dengue virus in Aedes aegypti

PLoS Negl Trop Dis. 2018 Mar 20;12(3):e0006339. doi: 10.1371/journal.pntd.0006339. eCollection 2018 Mar.

Abstract

Infection is a complex and dynamic process involving a population of invading microbes, the host and its responses, aimed at controlling the situation. Depending on the purpose and level of organization, infection at the organism level can be described by a process as simple as a coin toss, or as complex as a multi-factorial dynamic model; the former, for instance, may be adequate as a component of a population model, while the latter is necessary for a thorough description of the process beginning with a challenge with an infectious inoculum up to establishment or elimination of the pathogen. Experimental readouts in the laboratory are often static, snapshots of the process, assayed under some convenient experimental condition, and therefore cannot comprehensively describe the system. Different from the discrete treatment of infection in population models, or the descriptive summarized accounts of typical lab experiments, in this manuscript, infection is treated as a dynamic process dependent on the initial conditions of the infectious challenge, viral growth, and the host response along time. Here, experimental data is generated for multiple doses of type 1 dengue virus, and pathogen levels are recorded at different points in time for two populations of mosquitoes: either carrying endosymbiont bacteria Wolbachia or not. A dynamic microbe/host-response mathematical model is used to describe pathogen growth in the face of a host response like the immune system, and to infer model parameters for the two populations of insects, revealing a slight-but potentially important-protection conferred by the symbiont.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aedes / microbiology*
  • Aedes / virology*
  • Animals
  • Dengue / prevention & control
  • Dengue / transmission
  • Dengue Virus / physiology*
  • Host-Pathogen Interactions
  • Models, Biological*
  • Mosquito Vectors / microbiology*
  • Mosquito Vectors / virology*
  • Symbiosis
  • Virus Replication
  • Wolbachia / physiology*

Grants and funding

CSM was a beneficiary of a doctoral grant from the AXA Research Fund. MGMG was supported by Fundação para a Ciência e a Tecnologia (IF/01346/2014) and Coordenação de Aperfeicoamento de Pessoal de Nível Superior (0775/2014). RMF received funding from Grant Grupos Emergentes, Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (E 41/2013) The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.