Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence

Cara E. Brook; Mike Boots; Kartik Chandran; Andrew P. Dobson; Christian Drosten; Andrea L. Graham; Bryan T. Grenfell; Marcel A. Müller; Melinda Ng; Lin-Fa Wang; Anieke van Leeuwen

Finally, rVSV-G and rVSV-EBOV trials on PaKiT01 cells were best fit by models 287 assuming constitutive immunity, while rVSV-MARV infections on PaKiT01 were matched 288 equivalently by models assuming either induced or constitutive immunity-with induced models 289 favored over constitutive in AIC comparisons because one fewer parameter was estimated 290 File 4). In reality, we know that NPC1 receptor incompatibilities make PaKiT01 cell lines 328 constitutively refractory to rVSV-MARV infection (Ng and Chandran 2018) and that PaKiT01 329 cells also constitutively express the antiviral cytokine, IFN-. Model fitting results suggest that 330 this constitutive expression of IFN-may act more as a rapidly inducible immune response 331 following virus invasion than as a constitutive secretion of functional Nonetheless, as hypothesized, PaKiT01 cell lines were by far the most antiviral of any in our 333 study-with initial antiviral rates estimated several orders of magnitude higher than any others in 334 our study, under either induced or constitutive assumptions ( We found that R 0 was essentially unchanged across differing immune assumptions for RoNi/7.1 341 16 and Vero cells, for which the initial antiviral rate was low. In the case of PaKiT01 cells, a high 342 initial antiviral rate under either induced or constitutive immunity resulted in a correspondingly 343 high estimation of (and, consequently, R 0 ) which still produced the same epidemic curve that 344 resulted from the much lower estimates for and R 0 paired with absent immunity. These 345 findings suggest that antiviral immune responses protect host tissues against virus-induced cell 346 mortality and may facilitate the establishment of more rapid within-host transmission rates. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/696195 doi: bioRxiv preprint Finally, because the protective effect of antiviral cells is more clearly observable 364 spatially, we confirmed our results by simulating fitted time series in a spatially-explicit, 365 stochastic reconstruction of our mean field model. In spatial simulations, rates of antiviral 366 acquisition were fixed at fitted values for and derived from mean field estimates, while 367 transmission rates ( ) were fixed at values ten times greater than those estimated under mean 368 field conditions, accounting for the intensification of parameter thresholds permitting pathogen 369 invasion in local spatial interactions (see Materials and Methods; Videos 1-3; Figure 5 The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.