Model-based analysis of influenza A virus replication in genetically engineered cell lines elucidates the impact of host cell factors on key kinetic parameters of virus growth
Fig 4
Intracellular dynamics of viral RNA synthesis in different A549 cell lines.
Model fit (lines) to experimental data (circles ± standard deviation, n = 4 or single circles for FANCG, n = 2) of viral mRNA (panel 1), cRNA (panel 2), vRNA (panel 3) of segment 5 (encoding NP) in cell lines infected with A/PR/8/34 (H1N1) at MOI 50. Viral RNA synthesis rates and M1 binding rate were estimated by fitting the simulated number of the three viral RNA species to averaged segment-specific RT-qPCR data. To account for the offset in vRNA measurements caused by free viral RNAs in the seed virus we also implemented such offsets in our simulations with respect to the measurements obtained for parental A549 cells (A-F, blue), the transduction control (A, brown) and engineered cell lines overexpressing one of the following host cell factors: CEACAM6 (B, brown), FANCG (C, brown), NXF1 (D, brown), PLD2 (E, brown), XAB2 (F, brown). The asterisks indicate differences in RNA levels with respect to the parental A549 cell line, that were either noticeable, however, statistically not significant (* p ≤ 0.1), or significant (** p ≤ 0.05) determined by Kruskal-Wallis test.