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Tytuł pozycji:

A population of bang-bang switches of defective interfering particles makes within-host dynamics of dengue virus controllable.

Tytuł :
A population of bang-bang switches of defective interfering particles makes within-host dynamics of dengue virus controllable.
Autorzy :
Mapder T; School of Mathematical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia.; Australian Research Council Centre of Excellence for Mathematical and Statistical Frontiers, Queensland University of Technology, Brisbane, Queensland, Australia.
Clifford S; Centre for Mathematical Modelling of Infectious Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Aaskov J; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
Burrage K; School of Mathematical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia.; Australian Research Council Centre of Excellence for Mathematical and Statistical Frontiers, Queensland University of Technology, Brisbane, Queensland, Australia.; Department of Computer Science, University of Oxford, Oxford, United Kingdom.
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Źródło :
PLoS computational biology [PLoS Comput Biol] 2019 Nov 11; Vol. 15 (11), pp. e1006668. Date of Electronic Publication: 2019 Nov 11 (Print Publication: 2019).
Typ publikacji :
Journal Article; Research Support, U.S. Gov't, Non-P.H.S.
Język :
English
Imprint Name(s) :
Original Publication: San Francisco, CA : Public Library of Science, [2005]-
MeSH Terms :
Dengue/*virology
Dengue Virus/*physiology
Host Microbial Interactions/*physiology
Animals ; Culicidae ; Defective Viruses ; Humans ; Models, Theoretical ; Viral Load/physiology ; Viremia ; Virion ; Virus Replication
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Entry Date(s) :
Date Created: 20191112 Date Completed: 20200214 Latest Revision: 20200309
Update Code :
20211220
PubMed Central ID :
PMC6872170
DOI :
10.1371/journal.pcbi.1006668
PMID :
31710599
Czasopismo naukowe
The titre of virus in a dengue patient and the duration of this viraemia has a profound effect on whether or not a mosquito will become infected when it feeds on the patient and this, in turn, is a key driver of the magnitude of a dengue outbreak. The assessment of the heterogeneity of viral dynamics in dengue-infected patients and its precise treatment are still uncertain. Infection onset, patient physiology and immune response are thought to play major roles in the development of the viral load. Research has explored the interference and spontaneous generation of defective virus particles, but have not examined both the antibody and defective particles during natural infection. We explore the intrinsic variability in the within-host dynamics of viraemias for a population of patients using the method of population of models (POMs). A dataset from 208 patients is used to initially calibrate 20,000 models for the infection kinetics for each of the four dengue virus serotypes. The calibrated POMs suggests that naturally generated defective particles may interfere with the viraemia, but the generated defective virus particles are not adequate to reduce high fever and viraemia duration. The effect of adding excess defective dengue virus interfering particles to patients as a therapeutic is evaluated using the calibrated POMs in a bang-bang (on-off or two-step) optimal control setting. Bang-bang control is a class of binary feedback control that turns either 'ON' or 'OFF' at different time points, determined by the system feedback. Here, the bang-bang control estimates the mathematically optimal dose and duration of the intervention for each model in the POM set.
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