Spatial information allows inference of the prevalence of direct cell-to-cell viral infection.

Autor: Thomas Williams, James M McCaw, James M Osborne
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: PLoS Computational Biology, Vol 20, Iss 7, p e1012264 (2024)
Druh dokumentu: article
ISSN: 1553-734X
1553-7358
DOI: 10.1371/journal.pcbi.1012264
Popis: The role of direct cell-to-cell spread in viral infections-where virions spread between host and susceptible cells without needing to be secreted into the extracellular environment-has come to be understood as essential to the dynamics of medically significant viruses like hepatitis C and influenza. Recent work in both the experimental and mathematical modelling literature has attempted to quantify the prevalence of cell-to-cell infection compared to the conventional free virus route using a variety of methods and experimental data. However, estimates are subject to significant uncertainty and moreover rely on data collected by inhibiting one mode of infection by either chemical or physical factors, which may influence the other mode of infection to an extent which is difficult to quantify. In this work, we conduct a simulation-estimation study to probe the practical identifiability of the proportion of cell-to-cell infection, using two standard mathematical models and synthetic data that would likely be realistic to obtain in the laboratory. We show that this quantity cannot be estimated using non-spatial data alone, and that the collection of data which describes the spatial structure of the infection is necessary to infer the proportion of cell-to-cell infection. Our results provide guidance for the design of relevant experiments and mathematical tools for accurately inferring the prevalence of cell-to-cell infection in in vitro and in vivo contexts.
Databáze: Directory of Open Access Journals
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