Modeling Borna Disease Virus In Vitro Spread Reveals the Mode of Antiviral Effect Conferred by an Endogenous Bornavirus-Like Element

Kwang Su Kim; Yusuke Yamamoto; Shinji Nakaoka; Keizo Tomonaga; Shingo Iwami; Tomoyuki Honda

doi:10.1128/JVI.01204-20

DOI: 10.1128/JVI.01204-20

Article Figures & Data

Figures

Tables

Open in new tab
Download powerpoint
FIG 1
Cell viability and density dependency for intercellular BoDV-1 dynamics. Viabilities of OL, OL/itEBLN, and OL/BoDV cells were evaluated and are expressed as the means + five independent experiments in panel A. BoDV dynamics in OL cells are shown in panel B. Dots show the time course of experimental data for the numbers of uninfected cells (blue) and infected cells (red). The shaded region corresponds to 95% posterior predictive intervals, and the solid lines yield the mean for the full mathematical model with best-fit parameter estimates. Using all accepted MCMC parameter estimates from the time course experimental data sets, the distribution of e−α is shown in panel C. n.s., no significance (t test).
Open in new tab
Download powerpoint
FIG 2
Quantification of intercellular BoDV-1 dynamics in OL, OL/itEBLN, and OL/BoDV cells and the antiviral effect of itEBLN. OL, OL/itEBLN, and OL/BoDV cells were cocultured with OL/BoDV-GFP cells (target-to-seed ratio, 1,000:1). OL/itEBLN cells are OL cells stably expressing itEBLN. OL/BoDV cells are OL cells persistently infected with BoDV-1 strain huP2br. These cells were passaged once every 3 days and cultured in new wells at 4 × 10⁵ cells/well. BoDV-1 dynamics in OL, OL/itEBLN, and OL/BoDV cells are shown in panels A, B, and C, respectively. Dots show the time course of experimental data (the averaged data of at least four independent experiments) for the numbers of uninfected cells (darker) and infected cells (lighter). The shaded region corresponds to 95% posterior predictive intervals, and the solid lines indicate the mean for equation 1 with best-fit parameter estimates. In addition, the solid lines and shaded regions show the mean and 95% posterior predictive intervals of the predicted fraction of infected cells among total cells in panel D. Viabilities of OL and OL/BoDV cells during 3 days of coculture with OL/BoDV-GFP cells were evaluated and are expressed as the means + five independent experiments in panel E. Using all accepted MCMC parameter estimates from the time course experimental data sets, the distributions of the antiviral effect on BoDV-1 infection in OL/itEBLN and OL/BoDV cells (i.e., εEBLN and εBoDV) are shown in panel F. The dotted lines and dark and light bars show the mean, 95% credible interval, and whole estimations of the antiviral effects, respectively.
Open in new tab
Download powerpoint
FIG 3
Quantification of intracellular BoDV-1 dynamics in OL, OL/itEBLN, and OL/BoDV cells and antiviral effect of itEBLN. OL, OL/itEBLN, and OL/BoDV cells were transfected with plasmids expressing BoDV-1 N, P, L, and a Pol II-driven minigenome encoding GLuc. The luciferase activities in OL, OL/itEBLN, and OL/BoDV cells are shown together in panel A. Dots show the time course of experimental data for the luciferase activities of OL (green), OL/itEBLN (blue), and OL/BoDV (red) cells (the averaged data of at least three independent experiments), the shaded region corresponds to 95% posterior predictive intervals, and the solid lines indicate the mean for equation 2 with best-fit parameter estimates. The distributions of the inhibition rate on intracellular BoDV-1 replication in OL/itEBLN and OL/BoDV cells (i.e., ηEBLN and ηBoDV) are shown in panel B. The dotted lines and dark and light bars show the mean, 95% credible interval, and whole estimations of the antiviral effects, respectively.